3472 lines
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Entry
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- *600308 - AQUAPORIN 4; AQP4
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- OMIM
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<p>
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<span class="h4">*600308</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<a href="#geneFunction">Gene Function</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/600308">Table View</a>
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<li role="presentation">
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<a href="#seeAlso"><strong>See Also</strong></a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000171885;t=ENST00000383168" class="mim-tip-hint" title="Genome databases for vertebrates and other eukaryotic species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=361" class="mim-tip-hint" title="Detailed views of the complete genomes of selected organisms from vertebrates to protozoa." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Genome Viewer', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Genome Viewer</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=600308" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000171885;t=ENST00000383168" class="mim-tip-hint" title="Transcript-based views for coding and noncoding DNA." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl (MANE Select)</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001317384,NM_001317387,NM_001364286,NM_001364287,NM_001364289,NM_001650,NM_004028,XM_011525942" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001650" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq (MANE)', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq (MANE Select)</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=600308" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</span>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=02631&isoform_id=02631_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
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<div><a href="https://www.proteinatlas.org/search/AQP4" class="mim-tip-hint" title="The Human Protein Atlas contains information for a large majority of all human protein-coding genes regarding the expression and localization of the corresponding proteins based on both RNA and protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HumanProteinAtlas', 'domain': 'proteinatlas.org'})">Human Protein Atlas</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/protein/1072053,1236246,1680708,1680710,2506859,4502181,4755125,10503931,18490380,48675351,62087892,62896927,119621633,119621634,194379130,325451686,549514860,767998617,959071842,959077728,1401565944,1401565946,1401565948" class="mim-tip-hint" title="NCBI protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Protein', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Protein</a></div>
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<div><a href="https://www.uniprot.org/uniprotkb/P55087" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="http://biogps.org/#goto=genereport&id=361" class="mim-tip-hint" title="The Gene Portal Hub; customizable portal of gene and protein function information." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'BioGPS', 'domain': 'biogps.org'})">BioGPS</a></div>
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<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000171885;t=ENST00000383168" class="mim-tip-hint" title="Orthologs, paralogs, regulatory regions, and splice variants." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=AQP4" class="mim-tip-hint" title="The Human Genome Compendium; web-based cards integrating automatically mined information on human genes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneCards', 'domain': 'genecards.org'})">GeneCards</a></div>
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<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=AQP4" class="mim-tip-hint" title="Terms, defined using controlled vocabulary, representing gene product properties (biologic process, cellular component, molecular function) across species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneOntology', 'domain': 'amigo.geneontology.org'})">Gene Ontology</a></div>
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<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+361" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<dd><a href="http://v1.marrvel.org/search/gene/AQP4" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></dd>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/361" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr18&hgg_gene=ENST00000383168.9&hgg_start=26852038&hgg_end=26865803&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://medlineplus.gov/genetics/condition/neuromyelitis-optica" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=600308[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=600308[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/AQP4/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000171885" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.gwascentral.org/search?q=AQP4" class="mim-tip-hint" title="GWAS Central; summary level genotype-to-phenotype information from genetic association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Central', 'domain': 'gwascentral.org'})">GWAS Central </a></div>
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<div><a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=AQP4" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=AQP4&upstreamSize=0&downstreamSize=0&x=0&y=0" class="mim-tip-hint" title="National Heart, Lung, and Blood Institute Exome Variant Server." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NHLBI EVS', 'domain': 'evs.gs.washington.edu'})">NHLBI EVS</a></div>
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<div><a href="https://www.pharmgkb.org/gene/PA24922" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/gene/HGNC:637" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0015872.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:107387" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
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<div><a href="http://v1.marrvel.org/search/gene/AQP4#HomologGenesPanel" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></div>
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<div><a href="http://www.informatics.jax.org/marker/MGI:107387" class="mim-tip-hint" title="Mouse Genome Informatics; international database resource for the laboratory mouse, including integrated genetic, genomic, and biological data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Gene', 'domain': 'informatics.jax.org'})">MGI Mouse Gene</a></div>
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<div><a href="https://www.mmrrc.org/catalog/StrainCatalogSearchForm.php?search_query=" class="mim-tip-hint" title="Mutant Mouse Resource & Research Centers." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MMRRC', 'domain': 'mmrrc.org'})">MMRRC</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/361/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=361" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-040724-152" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:361" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=AQP4&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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600308
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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AQUAPORIN 4; AQP4
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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MERCURIAL-INSENSITIVE WATER CHANNEL; MIWC
|
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=AQP4" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">AQP4</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/18/107?start=-3&limit=10&highlight=107">18q11.2</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr18:26852038-26865803&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">18:26,852,038-26,865,803</a> </span>
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</em>
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</strong>
|
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
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<div style="margin-bottom: 10px;">
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<span class="h4 mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
|
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<span class="mim-font">
|
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<a href="/geneMap/18/107?start=-3&limit=10&highlight=107">
|
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18q11.2
|
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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?Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting
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<span class="mim-tip-hint" title="A question mark (?) indicates that the relationship between the phenotype and gene is provisional">
|
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<span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span>
|
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</span>
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<a href="/entry/620448"> 620448 </a>
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/600308" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/600308" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
|
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4>
|
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|
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<span class="mim-font">
|
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
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<strong>TEXT</strong>
|
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</span>
|
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</span>
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</h4>
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<div>
|
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<a id="description" class="mim-anchor"></a>
|
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
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<span class="mim-font">
|
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<strong>Description</strong>
|
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</span>
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</h4>
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</div>
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<div id="mimDescriptionFold" class="collapse in ">
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<span class="mim-text-font">
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<p>The aquaporins are a family of water-selective membrane channels found in animals, plants, and microorganisms. AQP4 is the predominant water channel in the brain and has an important role in brain water homeostasis. It is abundant in mammalian brain and is concentrated in astrocytic foot processes at the blood-brain barrier (<a href="#1" class="mim-tip-reference" title="Amiry-Moghaddam, M., Otsuka, T., Hurn, P. D., Traystman, R. J., Haug, F.-M., Froehner, S. C., Adams, M. E., Neely, J. D., Agre, P., Ottersen, O. P., Bhardwaj, A. <strong>An alpha-syntrophin-dependent pool of AQP4 in astroglial end-feet confers bidirectional water flow between blood and brain.</strong> Proc. Nat. Acad. Sci. 100: 2106-2111, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12578959/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12578959</a>] [<a href="https://doi.org/10.1073/pnas.0437946100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12578959">Amiry-Moghaddam et al., 2003</a>; <a href="#9" class="mim-tip-reference" title="Lennon, V. A., Kryzer, T. J., Pittock, S. J., Verkman, A. S., Hinson, S. R. <strong>IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel.</strong> J. Exp. Med. 202: 473-477, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16087714/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16087714</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16087714[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1084/jem.20050304" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16087714">Lennon et al., 2005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12578959+16087714" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>See also aquaporin-1 (AQP1; <a href="/entry/107776">107776</a>), also known as CHIP (for 'channel-forming integral membrane protein'), which was the first protein shown to function as a molecular water channel and is naturally expressed in mammalian red cells, renal proximal tubules, and other water-permeable epithelia. AQP1 is abundant in the choroid plexus. AQP2 (<a href="/entry/107777">107777</a>) is the vasopressin-regulated water channel in renal collecting ducts and is the site of mutations in some forms of nephrogenic diabetes insipidus. AQP3 (<a href="/entry/600170">600170</a>) is the water channel in basolateral membranes of renal medullary collecting ducts.</p>
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<p>By homology cloning, <a href="#5" class="mim-tip-reference" title="Jung, J. S., Bhat, R. V., Preston, G. M., Guggino, W. B., Baraban, J. M., Agre, P. <strong>Molecular characterization of an aquaporin cDNA from brain: candidate osmoreceptor and regulator of water balance.</strong> Proc. Nat. Acad. Sci. 91: 13052-13056, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7528931/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7528931</a>] [<a href="https://doi.org/10.1073/pnas.91.26.13052" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7528931">Jung et al. (1994)</a> isolated an AQP4 cDNA from a rat brain cDNA library and established its function and distribution. Like AQP1, the deduced polypeptide has 6 putative transmembrane domains but lacks cysteines at the known mercurial-sensitive sites. Two initiation sites were identified encoding polypeptides of 301 and 323 amino acids; expression of each in Xenopus oocytes conferred a 20-fold increase in osmotic water permeability not blocked by 1 mM HgCl(2), even after substitution of cysteine at the predicted mercury-sensitive site. Northern blot analysis and RNase protection demonstrated the mRNA to be abundant in mature rat brain but only weakly detectable in eye, kidney, intestine, and lung. In situ hybridization of brain localized the mRNA to ependymal cells lining the aqueduct, glial cells forming the edge of the cerebral cortex and brainstem, vasopressin-secretory neurons in supraoptic and paraventricular nuclei of hypothalamus, and Purkinje cells of cerebellum. Its distinctive expression pattern implicated this fourth mammalian member of the aquaporin water channel family as the osmoreceptor that regulates body water balance and mediates water flow within the central nervous system. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7528931" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Several mammalian water channels have been cloned, most of which are inhibited by mercurials. <a href="#27" class="mim-tip-reference" title="Yang, B., Ma, T., Verkman, A. S. <strong>cDNA cloning, gene organization, and chromosomal localization of a human mercurial insensitive water channel: evidence for distinct transcriptional units.</strong> J. Biol. Chem. 270: 22907-22913, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7559426/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7559426</a>] [<a href="https://doi.org/10.1074/jbc.270.39.22907" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7559426">Yang et al. (1995)</a> cloned 2 distinct human cDNAs encoding AQP4, which they called mercurial-insensitive water channel (MIWC), from a fetal brain cDNA library. The longest open reading frame encoded 301 amino acids with 94% identity to rat MIWC. Expression of MIWC cRNAs in Xenopus oocytes increased osmotic water permeability by 10- to 20-fold in a mercurial-insensitive manner. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7559426" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Ma, T., Yang, B., Verkman, A. S. <strong>Gene structure, cDNA cloning, and expression of a mouse mercurial-insensitive water channel.</strong> Genomics 33: 382-388, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8660998/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8660998</a>] [<a href="https://doi.org/10.1006/geno.1996.0214" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8660998">Ma et al. (1996)</a> cloned 3 mouse MIWC cDNAs from a brain library. The predicted proteins differed at their amino termini as a consequence of alternative splicing. The investigators also characterized the expression patterns of the transcripts and studied the expressed protein product by cRNA microinjection into Xenopus oocytes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8660998" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Sapkota, D., Florian, C., Doherty, B. M., White, K. M., Reardon, K. M., Ge, X., Garbow, J. R., Yuede, C. M., Cirrito, J. R., Dougherty, J. D. <strong>Aqp4 stop codon readthrough facilitates amyloid-beta clearance from the brain.</strong> Brain 145: 2982-2990, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36001414/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36001414</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=36001414[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/brain/awac199" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="36001414">Sapkota et al. (2022)</a> noted that readthrough of the stop codon of mouse Aqp4 produces an extended Aqp4 isoform, Aqp4X. Aqp4X is exclusively perivascular within astrocytic endfeet in mouse brain, whereas canonical Aqp4 localizes to parenchyma away from blood vessels. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36001414" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Analysis of MIWC genomic clones by <a href="#27" class="mim-tip-reference" title="Yang, B., Ma, T., Verkman, A. S. <strong>cDNA cloning, gene organization, and chromosomal localization of a human mercurial insensitive water channel: evidence for distinct transcriptional units.</strong> J. Biol. Chem. 270: 22907-22913, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7559426/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7559426</a>] [<a href="https://doi.org/10.1074/jbc.270.39.22907" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7559426">Yang et al. (1995)</a> indicated 2 distinct but overlapping transcription units from which multiple MIWC mRNAs are transcribed. Three introns were present. Genomic Southern blot analysis indicated the presence of a single MIWC gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7559426" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Lu, M., Lee, M. D., Smith, B. L., Jung, J. S., Agre, P., Verdijk, M. A. J., Merkx, G., Rijss, J. P. L., Deen, P. M. T. <strong>The human AQP4 gene: definition of the locus encoding two water channel polypeptides in brain.</strong> Proc. Nat. Acad. Sci. 93: 10908-10912, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8855281/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8855281</a>] [<a href="https://doi.org/10.1073/pnas.93.20.10908" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8855281">Lu et al. (1996)</a> reported the isolation and characterization of the human AQP4 cDNAs and genomic DNA. Similar to other aquaporins, the AQP4 gene is composed of 4 exons encoding 127, 55, 27, and 92 amino acids separated by introns of 0.8, 0.3, and 5.2 kb. Unlike other aquaporins, an alternative coding initiation sequence (designated exon 0) was located 2.7 kb upstream of exon 1. When spliced together, M1 and the subsequent 10 amino acids are encoded by exon 0; the next 11 amino acids and M23 are encoded by exon 1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8855281" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By chromosome-specific PCR and in situ hybridization, <a href="#27" class="mim-tip-reference" title="Yang, B., Ma, T., Verkman, A. S. <strong>cDNA cloning, gene organization, and chromosomal localization of a human mercurial insensitive water channel: evidence for distinct transcriptional units.</strong> J. Biol. Chem. 270: 22907-22913, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7559426/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7559426</a>] [<a href="https://doi.org/10.1074/jbc.270.39.22907" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7559426">Yang et al. (1995)</a> localized the MIWC gene to chromosome 18q22. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7559426" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By fluorescence in situ hybridization, <a href="#12" class="mim-tip-reference" title="Lu, M., Lee, M. D., Smith, B. L., Jung, J. S., Agre, P., Verdijk, M. A. J., Merkx, G., Rijss, J. P. L., Deen, P. M. T. <strong>The human AQP4 gene: definition of the locus encoding two water channel polypeptides in brain.</strong> Proc. Nat. Acad. Sci. 93: 10908-10912, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8855281/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8855281</a>] [<a href="https://doi.org/10.1073/pnas.93.20.10908" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8855281">Lu et al. (1996)</a> determined that the AQP4 gene maps to 18q11.2-q12.1. By interspecific backcross analysis, <a href="#23" class="mim-tip-reference" title="Turtzo, L. C., Lee, M. D., Lu, M., Smith, B. L., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., Agre, P. <strong>Cloning and chromosomal localization of mouse aquaporin 4: exclusion of a candidate mutant phenotype, ataxia.</strong> Genomics 41: 267-270, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9143504/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9143504</a>] [<a href="https://doi.org/10.1006/geno.1997.4641" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9143504">Turtzo et al. (1997)</a> mapped the mouse Aqp4 gene to the proximal region of chromosome 18. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8855281+9143504" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Analyzing the expression of AQP4 in mammalian skeletal muscle, <a href="#4" class="mim-tip-reference" title="Frigeri, A., Nicchia, G. P., Verbavatz, J. M., Valenti, G., Svelto, M. <strong>Expression of aquaporin-4 in fast-twitch fibers of mammalian skeletal muscle.</strong> J. Clin. Invest. 102: 695-703, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9710437/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9710437</a>] [<a href="https://doi.org/10.1172/JCI2545" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9710437">Frigeri et al. (1998)</a> found that, in immunohistochemical experiments, affinity-purified AQP4 antibodies stained selectively the sarcolemma of fast-twitch fibers. By immunogold electron microscopy, little or no intracellular labeling was detected. Other experiments provided for the first time evidence for the expression of an aquaporin in skeletal muscle correlated to a specific fiber-type metabolism. <a href="#4" class="mim-tip-reference" title="Frigeri, A., Nicchia, G. P., Verbavatz, J. M., Valenti, G., Svelto, M. <strong>Expression of aquaporin-4 in fast-twitch fibers of mammalian skeletal muscle.</strong> J. Clin. Invest. 102: 695-703, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9710437/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9710437</a>] [<a href="https://doi.org/10.1172/JCI2545" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9710437">Frigeri et al. (1998)</a> analyzed AQP4 expression in skeletal muscle of mdx mice; immunofluorescence experiments showed a marked reduction of AQP4 expression, suggesting a critical role in the membrane alteration of Duchenne muscular dystrophy (DMD; <a href="/entry/310200">310200</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9710437" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#26" class="mim-tip-reference" title="Wakayama, Y., Jimi, T., Inoue, M., Kojima, H., Murahashi, M., Kumagai, T., Yamashita, S., Hara, H., Shibuya, S. <strong>Reduced aquaporin 4 expression in the muscle plasma membrane of patients with Duchenne muscular dystrophy.</strong> Arch. Neurol. 59: 431-437, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11890849/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11890849</a>] [<a href="https://doi.org/10.1001/archneur.59.3.431" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11890849">Wakayama et al. (2002)</a> analyzed skeletal muscle samples from 6 patients with DMD and found markedly reduced AQP4 expression by immunohistochemical staining and markedly decreased levels of AQP4 mRNA as measured by RT-PCR, compared to controls. Genomic analysis of the AQP4 gene revealed no abnormalities. The authors concluded that the reduced mRNA was due to either decreased transcription or increased degradation of the message. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11890849" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Immunocytochemistry revealed strong AQP4 water channel expression in Muller cells in mouse retina and in fibrous astrocytes in optic nerve. <a href="#10" class="mim-tip-reference" title="Li, J., Patil, R. V., Verkman, A. S. <strong>Mildly abnormal retinal function in transgenic mice without Muller cell aquaporin-4 water channels.</strong> Invest. Ophthal. Vis. Sci. 43: 573-579, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11818406/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11818406</a>]" pmid="11818406">Li et al. (2002)</a> compared electroretinograms and retinal morphology in wildtype mice and transgenic knockout mice with no Aqp4. Significantly reduced electroretinogram b-wave potentials were recorded in 10-month-old null mice with smaller changes in 1-month-old mice. Morphologic analysis of retina by light and electron microscopy showed no differences in retinal ultrastructure. That retinal function was mildly impaired in Aqp4-null mice suggested a role for Aqp4 in Muller cell fluid balance. The authors suggested that AQP4 expression in supportive cells in the nervous system facilitates neural signal transduction in nearby electrically excitable cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11818406" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Manley, G. T., Fujimura, M., Ma, T., Noshita, N., Filiz, F., Bollen, A. W., Chan, P., Verkman, A. S. <strong>Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke.</strong> Nature Med. 6: 159-163, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10655103/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10655103</a>] [<a href="https://doi.org/10.1038/72256" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10655103">Manley et al. (2000)</a> reported that AQP4 negatively influences the outcome of brain edema. Other studies also suggested that AQP4 contributes to the development of brain edema (<a href="#25" class="mim-tip-reference" title="Vajda, Z., Promeneur, D., Doczi, T., Sulyok, E., Frokiaer, J., Ottersen, O. P., Neilsen, S. <strong>Increased aquaporin-4 immunoreactivity in rat brain in response to systemic hyponatremia.</strong> Biochem. Biophys. Res. Commun. 270: 495-503, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10753653/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10753653</a>] [<a href="https://doi.org/10.1006/bbrc.2000.2472" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10753653">Vajda et al., 2000</a>). <a href="#24" class="mim-tip-reference" title="Vajda, Z., Pedersen, M., Fuchtbauer, E.-M., Wertz, K., Stodkilde-Jorgensen, H., Sulyok, E., Doczi, T., Neely, J. D., Agre, P., Frokier, J., Nielsen, S. <strong>Delayed onset of brain edema and mislocalization of aquaporin-4 in dystrophin-null transgenic mice.</strong> Proc. Nat. Acad. Sci. 99: 13131-13136, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12232046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12232046</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12232046[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.192457099" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12232046">Vajda et al. (2002)</a> performed studies in dystrophin (<a href="/entry/300377">300377</a>) null transgenic mice indicating that dystrophin is necessary for polarized distribution of AQP4 protein in brain where facilitated movements of water occur across the blood-brain barrier and cerebrospinal fluid-brain interface. The results predicted that interference with the subcellular localization of AQP4 may have therapeutic potential for delaying the onset of impending brain edema. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10655103+10753653+12232046" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Recovery from neuronal activation requires rapid clearance of potassium ions and restoration of osmotic equilibrium. The predominant water channel protein in brain, AQP4, is concentrated in the astrocyte endfeet membranes adjacent to blood vessels in neocortex and cerebellum by association with alpha-syntrophin (SNTA1; <a href="/entry/601017">601017</a>). <a href="#2" class="mim-tip-reference" title="Amiry-Moghaddam, M., Williamson, A., Palomba, M., Eid, T., de Lanerolle, N. C., Nagelhus, E. A., Adams, M. E., Froehner, S. C., Agre, P., Ottersen, O. P. <strong>Delayed K(+) clearance associated with aquaporin-4 mislocalization: phenotypic defects in brains of alpha-syntrophin-null mice.</strong> Proc. Nat. Acad. Sci. 100: 13615-13620, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14597704/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14597704</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14597704[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.2336064100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14597704">Amiry-Moghaddam et al. (2003)</a> used immunogold electron microscopy to compare hippocampus of wildtype and alpha-syntrophin-null mice. They found that less than 10% of Aqp4 immunogold labeling was retained in the perivascular astrocyte endfeet membranes of the null mice, whereas labeling of the inwardly rectifying potassium channel Kir4.1 (<a href="/entry/602208">602208</a>) was largely unchanged. Several other experiments, including the demonstration that the intensity of hyperthermia-induced epileptic seizures was increased in approximately half of the null mice, led <a href="#2" class="mim-tip-reference" title="Amiry-Moghaddam, M., Williamson, A., Palomba, M., Eid, T., de Lanerolle, N. C., Nagelhus, E. A., Adams, M. E., Froehner, S. C., Agre, P., Ottersen, O. P. <strong>Delayed K(+) clearance associated with aquaporin-4 mislocalization: phenotypic defects in brains of alpha-syntrophin-null mice.</strong> Proc. Nat. Acad. Sci. 100: 13615-13620, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14597704/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14597704</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14597704[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.2336064100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14597704">Amiry-Moghaddam et al. (2003)</a> to propose that water flux through perivascular AQP4 is needed to sustain efficient removal of potassium ions after neuronal activation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14597704" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using quantitative immunogold electron microscopy, <a href="#3" class="mim-tip-reference" title="Eid, T., Lee, T.-S. W., Thomas, M. J., Amiry-Moghaddam, M., Bjornsen, L. P., Spencer, D. D., Agre, P., Ottersen, O. P., de Lanerolle, N. C. <strong>Loss of perivascular aquaporin 4 may underlie deficient water and K(+) homeostasis in the human epileptogenic hippocampus.</strong> Proc. Nat. Acad. Sci. 102: 1193-1198, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15657133/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15657133</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15657133[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0409308102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15657133">Eid et al. (2005)</a> showed that the density of AQP4 along the perivascular membrane domain of astrocytes was decreased by an average of 44% in area CA1 of hippocampi from 24 patients with mesial temporal lobe epilepsy with hippocampal sclerosis compared to controls. There was no difference in AQP4 density on the astrocyte membrane facing the neuropil. Further studies suggested that the loss of AQP4 was due to disruption of the dystrophin complex. Western blot analysis showed a significant increase in overall AQP4 in mesial temporal lobe epilepsy tissue compared to controls, consistent with the proliferation of astrocytes typical of hippocampal sclerosis. <a href="#3" class="mim-tip-reference" title="Eid, T., Lee, T.-S. W., Thomas, M. J., Amiry-Moghaddam, M., Bjornsen, L. P., Spencer, D. D., Agre, P., Ottersen, O. P., de Lanerolle, N. C. <strong>Loss of perivascular aquaporin 4 may underlie deficient water and K(+) homeostasis in the human epileptogenic hippocampus.</strong> Proc. Nat. Acad. Sci. 102: 1193-1198, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15657133/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15657133</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15657133[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0409308102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15657133">Eid et al. (2005)</a> postulated that the loss of perivascular AQP4 in mesial temporal lobe epilepsy results in a perturbed flux of water through astrocytes, leading to impaired buffering of extracellular potassium and an increased propensity for seizures. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15657133" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Lennon, V. A., Kryzer, T. J., Pittock, S. J., Verkman, A. S., Hinson, S. R. <strong>IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel.</strong> J. Exp. Med. 202: 473-477, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16087714/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16087714</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16087714[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1084/jem.20050304" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16087714">Lennon et al. (2005)</a> found that a serum IgG autoantibody specific for neuromyelitis optica (NMO) binds selectively to the AQP4 channel. NMO is an inflammatory demyelinating disease that selectively affects optic nerves and spinal cord and is considered a severe variant of multiple sclerosis (MS; <a href="/entry/126200">126200</a>), although the prognosis and treatment differ from MS. In 8 patients with NMO who were seropositive for NMO-IgG autoantibodies, <a href="#18" class="mim-tip-reference" title="Pittock, S. J., Weinshenker, B. G., Lucchinetti, C. F., Wingerchuk, D. M., Corboy, J. R., Lennon, V. A. <strong>Neuromyelitis optica brain lesions localized at sites of high aquaporin 4 expression.</strong> Arch. Neurol. 63: 964-968, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16831965/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16831965</a>] [<a href="https://doi.org/10.1001/archneur.63.7.964" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16831965">Pittock et al. (2006)</a> observed recurring and distinctive brain MRI abnormalities in hypothalamic and periventricular areas that corresponded to brain regions of high AQP4 expression. The findings further supported the hypothesis that AQP4-IgG plays a pathogenic role in NMO. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16831965+16087714" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="McKeon, A., Lennon, V. A., Lotze, T., Tenenbaum, S., Ness, J. M., Rensel, M., Kuntz, N. L., Fryer, J. P., Homburger, H., Hunter, J., Weinshenker, B. G., Krecke, K., Lucchinetti, C. F., Pittock, S. J. <strong>CNS aquaporin-4 autoimmunity in children.</strong> Neurology 71: 93-100, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18509092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18509092</a>] [<a href="https://doi.org/10.1212/01.wnl.0000314832.24682.c6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18509092">McKeon et al. (2008)</a> identified 88 consecutive children who were NMO-IgG seropositive; clinical information was available for 58. The median age at symptom onset was 12 years (range, 4 to 18). Fifty-seven (98%) had attacks of either optic neuritis (83%) or transverse myelitis (78%), or both. Twenty-six (45%) had episodic cerebral symptoms, including encephalopathy, ophthalmoparesis, ataxia, seizures, intractable vomiting, or hiccups. Thirty-eight (68%) had brain MRI abnormalities, predominantly involving periventricular areas, but including other areas as well. Additional autoantibodies were detected in 57 (76%) of 75 patients, and 16 (42%) of 38 had a coexisting autoimmune disorder. Attacks were recurrent in 54 patients at 12 months follow-up. <a href="#15" class="mim-tip-reference" title="McKeon, A., Lennon, V. A., Lotze, T., Tenenbaum, S., Ness, J. M., Rensel, M., Kuntz, N. L., Fryer, J. P., Homburger, H., Hunter, J., Weinshenker, B. G., Krecke, K., Lucchinetti, C. F., Pittock, S. J. <strong>CNS aquaporin-4 autoimmunity in children.</strong> Neurology 71: 93-100, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18509092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18509092</a>] [<a href="https://doi.org/10.1212/01.wnl.0000314832.24682.c6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18509092">McKeon et al. (2008)</a> concluded that AQP4 autoimmunity is a distinctive recurrent and widespread inflammatory CNS disease in children. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18509092" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>AQP1 and AQP4 regulate the movement of water in ischemic brain, and they appear to play a role in cerebral edema. By searching a microRNA (miRNA) database for miRNAs that could target the 3-prime UTRs of AQP1 and AQP4, <a href="#21" class="mim-tip-reference" title="Sepramaniam, S., Armugam, A., Lim, K. Y., Karolina, D. S., Swaminathan, P., Tan, J. R., Jeyaseelan, K. <strong>MicroRNA 320a functions as a novel endogenous modulator of aquaporins 1 and 4 as well as a potential therapeutic target in cerebral ischemia.</strong> J. Biol. Chem. 285: 29223-29230, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20628061/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20628061</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20628061[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1074/jbc.M110.144576" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20628061">Sepramaniam et al. (2010)</a> identified MIR320A (<a href="/entry/614112">614112</a>). Knockdown of MIR320A via anti-MIR320A in a human astrocytoma cell line upregulated expression of AQP1 and AQP4 mRNA and protein. Conversely, overexpression of pre-MIR320A reduced expression of AQP1 and AQP4 mRNA and protein. Reporter gene assays confirmed direct targeting of the 3-prime UTRs of AQP1 and AQP4 by MIR320A. Astrocytes subjected to oxygen and glucose deprivation, which mimics the ischemic environment, downregulated expression of MIR320A, concomitant with upregulated expression of AQP1 and AQP4. Administration of anti-MIR320A to rats following occlusion of the middle cerebral artery reduced the infarct volume, whereas pre-MIR320A caused a further increase in infarct volume. <a href="#21" class="mim-tip-reference" title="Sepramaniam, S., Armugam, A., Lim, K. Y., Karolina, D. S., Swaminathan, P., Tan, J. R., Jeyaseelan, K. <strong>MicroRNA 320a functions as a novel endogenous modulator of aquaporins 1 and 4 as well as a potential therapeutic target in cerebral ischemia.</strong> J. Biol. Chem. 285: 29223-29230, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20628061/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20628061</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20628061[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1074/jbc.M110.144576" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20628061">Sepramaniam et al. (2010)</a> concluded that MIR320 modulates AQP1 and AQP2 and may have a role in cerebral ischemia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20628061" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using various methods, <a href="#8" class="mim-tip-reference" title="Lanciotti, A., Brignone, M. S., Molinari, P., Visentin, S., De Nuccio, C., Macchia, G., Aiello, C., Bertini, E., Aloisi, F., Petrucci, T. C., Ambrosini, E. <strong>Megalencephalic leukoencephalopathy with subcortical cysts protein 1 functionally cooperates with the TRPV4 cation channel to activate the response of astrocytes to osmotic stress: dysregulation by pathological mutations.</strong> Hum. Molec. Genet. 21: 2166-2180, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22328087/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22328087</a>] [<a href="https://doi.org/10.1093/hmg/dds032" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22328087">Lanciotti et al. (2012)</a> found that MLC1 (<a href="/entry/605908">605908</a>), TRPV4 (<a href="/entry/605427">605427</a>), HEPACAM (<a href="/entry/611642">611642</a>), syntrophin, caveolin-1 (CAV1; <a href="/entry/601047">601047</a>), Kir4.1, and AQP4 assembled into an Na,K-ATPase-associated multiprotein complex. In rat and human astrocyte cell lines, this Na,K-ATPase complex mediated swelling-induced cytosolic calcium increase and volume recovery in response to hyposmotic stress. MLC1 associated directly with the Na,K-ATPase beta-1 subunit (ATP1B1; <a href="/entry/182330">182330</a>), and plasma membrane expression of MLC1 was required for assembly of the Na,K-ATPase complex. TRPV4 was required for calcium influx, and AQP4 was recruited to the complex following hyposmotic stress. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22328087" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In 2 sibs (P4 and P5), born of consanguineous parents, with remitting megalencephalic leukoencephalopathy with subcortical cysts-4 (MLC4; <a href="/entry/620448">620448</a>), <a href="#17" class="mim-tip-reference" title="Passchier, E. M. J., Kerst, S., Brouwers, E., Hamilton, E. M. C., Bisseling, Q., Bugiani, M., Waisfisz, Q., Kitchen, P., Unger, L., Breur, M., Hoogterp, L., de Vries, S. I., and 12 others. <strong>Aquaporin-4 and GPRC5B: old and new players in controlling brain oedema.</strong> Brain 146: 3444-3454, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/37143309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">37143309</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=37143309[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/brain/awad146" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="37143309">Passchier et al. (2023)</a> identified a homozygous missense mutation in the AQP4 gene (A215T; <a href="#0001">600308.0001</a>) affecting the second NPA motif that forms part of the channel pore. The mutation, which was found by a combination of homozygosity mapping and candidate gene sequencing, segregated with the disorder in the family. Western blot analysis of MDCK cells transfected with the mutation showed no detectable expression of mutant AQP4, suggesting that the mutant protein is unstable and rapidly degraded. Functional studies showed no change in swelling and shrinking rate constants when the cells with the A215T mutation were exposed to hypotonic or hypertonic shock, whereas cells with wildtype AQP4 responded with increased swelling and shrinking under the same conditions. Overexpression of the A215T mutation in HEK293 cells showed detectable, but reduced, AQP4 membrane localization compared to controls. Mutant AQP4 formed large intracellular protein aggregates, and there was a 60% reduction in membrane localization compared to wildtype. Overexpression of mutant AQP4 increased swelling and shrinking in response to shock, but the rates were significantly reduced compared to wildtype. The findings suggested that mutant A215T AQP4 reaching the cell membrane retains some residual water channel function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=37143309" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#11" class="mim-tip-reference" title="Li, J., Verkman, A. S. <strong>Impaired hearing in mice lacking aquaporin-4 water channels.</strong> J. Biol. Chem. 276: 31233-31237, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11406631/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11406631</a>] [<a href="https://doi.org/10.1074/jbc.M104368200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11406631">Li and Verkman (2001)</a> noted that several of the aquaporins localize in the mammalian inner ear and are proposed to play a role in hearing. They localized mouse Aqp1 in fibrocytes in the spiral ligament and Aqp4 in supporting epithelial cells in the organ of Corti. <a href="#11" class="mim-tip-reference" title="Li, J., Verkman, A. S. <strong>Impaired hearing in mice lacking aquaporin-4 water channels.</strong> J. Biol. Chem. 276: 31233-31237, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11406631/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11406631</a>] [<a href="https://doi.org/10.1074/jbc.M104368200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11406631">Li and Verkman (2001)</a> developed aquaporin-null mice, targeting Aqp1, Aqp3, Aqp4, and Aqp5 (<a href="/entry/600442">600442</a>). They found that the threshold auditory brainstem response to a click stimulus was significantly increased in Aqp4-null mice. The hearing impairment in these mice was frequency independent and was not accompanied by anatomical abnormalities. They found no hearing impairment in any of the other aquaporin-null mice. By immunolocalization studies in mouse retina, <a href="#10" class="mim-tip-reference" title="Li, J., Patil, R. V., Verkman, A. S. <strong>Mildly abnormal retinal function in transgenic mice without Muller cell aquaporin-4 water channels.</strong> Invest. Ophthal. Vis. Sci. 43: 573-579, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11818406/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11818406</a>]" pmid="11818406">Li et al. (2002)</a> localized Aqp4 in Muller cells of the retina and in fibrous astrocytes of the optic nerve. Aqp4-null mice showed no difference in retinal ultrastructure, but electroretinograms of Aqp4-null mice indicated mildly impaired retinal function. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11406631+11818406" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By immunolocalization of Aqp4 in mouse and rat inner ear, <a href="#16" class="mim-tip-reference" title="Mhatre, A. N., Stern, R. E., Li, J., Lalwani, A. K. <strong>Aquaporin 4 expression in the mammalian inner ear and its role in hearing.</strong> Biochem. Biophys. Res. Commun. 297: 987-996, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12359252/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12359252</a>] [<a href="https://doi.org/10.1016/s0006-291x(02)02296-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12359252">Mhatre et al. (2002)</a> found that Aqp4 is expressed within the epithelia surrounding sensory cells of the auditory and vestibular sensory organs and in glial cells surrounding the auditory nerve. Aqp4 knockout mice demonstrated impaired hearing. Neural conduction times in knockout mice were normal, suggesting that cochlear dysfunction was the cause of hearing impairment. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12359252" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>AQP4 is anchored at the perivascular and subpial membranes by its C terminus to alpha-syntrophin (SNTA1; <a href="/entry/601017">601017</a>), an adaptor protein associated with dystrophin. To test functions of the perivascular AQP4 pool, <a href="#1" class="mim-tip-reference" title="Amiry-Moghaddam, M., Otsuka, T., Hurn, P. D., Traystman, R. J., Haug, F.-M., Froehner, S. C., Adams, M. E., Neely, J. D., Agre, P., Ottersen, O. P., Bhardwaj, A. <strong>An alpha-syntrophin-dependent pool of AQP4 in astroglial end-feet confers bidirectional water flow between blood and brain.</strong> Proc. Nat. Acad. Sci. 100: 2106-2111, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12578959/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12578959</a>] [<a href="https://doi.org/10.1073/pnas.0437946100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12578959">Amiry-Moghaddam et al. (2003)</a> studied mice homozygous for targeted disruption of SNTA1. These animals showed a marked loss of Aqp4 from perivascular and subpial membranes but no decrease in other membrane domains, as judged by quantitative immunogold electron microscopy. In the basal state, perivascular and subpial astroglial endfeet were swollen in brains of SNTA1 -/- mice compared to wildtype mice, suggesting reduced clearance of water generated by brain metabolism. When stressed by transient cerebral ischemia, brain edema was attenuated in these same null mice, indicative of reduced water influx. These studies identified a specific, syntrophin-dependent AQP4 pool that is expressed at distinct membrane domains and mediates bidirectional transport of water across the brain-blood interface. The anchoring of AQP4 to SNTA1 may be a target for treatment of brain edema, but therapeutic manipulations of AQP4 must consider the bidirectional water flux through this molecule. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12578959" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Compression spinal cord injury, caused by bilateral constant pressure, is thought to cause mechanical disruption of cells and ischemia and is a model of cytotoxic edema. In contrast, contusion spinal cord injury, caused by impact, causes disruption of blood vessels and is a model of vasogenic edema. <a href="#19" class="mim-tip-reference" title="Saadoun, S., Bell, B. A., Verkman, A. S., Papadopoulos, M. C. <strong>Greatly improved neurological outcome after spinal cord compression injury in AQP4-deficient mice.</strong> Brain 131: 1087-1098, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18267965/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18267965</a>] [<a href="https://doi.org/10.1093/brain/awn014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18267965">Saadoun et al. (2008)</a> found that Aqp4-null mice had greatly improved neurologic outcome after spinal cord compression injury compared to wildtype mice. Aqp4-null mice had less hindlimb weakness, better motor and sensory indices, and less neuronal death, myelin vacuolation, and swelling and pressure in the spinal cord compared to wildtype mice. In wildtype mice, Aqp4 immunoreactivity at the injury site was increased in gray and white matter at 48 hours. The findings suggested that Aqp4 provides a major route for excess water entry into the injured spinal cord after compression injury, which in turn causes spinal cord swelling, edema, elevated spinal cord pressure, and neurologic impairment. <a href="#19" class="mim-tip-reference" title="Saadoun, S., Bell, B. A., Verkman, A. S., Papadopoulos, M. C. <strong>Greatly improved neurological outcome after spinal cord compression injury in AQP4-deficient mice.</strong> Brain 131: 1087-1098, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18267965/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18267965</a>] [<a href="https://doi.org/10.1093/brain/awn014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18267965">Saadoun et al. (2008)</a> suggested that inhibition or downregulation of Aqp4 could be an early neuroprotective maneuver in compression spinal cord injury by reducing cytotoxic edema. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18267965" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In contrast, <a href="#7" class="mim-tip-reference" title="Kimura, A., Hsu, M., Seldin, M., Verkman, A. S., Scharfman, H. E., Binder, D. K. <strong>Protective role of aquaporin-4 water channels after contusion spinal cord injury.</strong> Ann. Neurol. 67: 794-801, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20517941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20517941</a>] [<a href="https://doi.org/10.1002/ana.22023" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20517941">Kimura et al. (2010)</a> found that Aqp4-null mice had more functional deterioration after contusion spinal cord injury than wildtype mice. Aqp4-null mice had worse motor recovery, prolonged bladder dysfunction, and greater lesion volume, neuronal loss, cyst formation, and edema in the spinal cord compared to wildtype mice after contusion spinal cord injury. The results suggested that Aqp4 plays a protective role after contusion spinal cord injury by facilitating the clearance of excess tissue water. The studies highlighted the bidirectional role of AQP4 in the brain: AQP4 is a major route for brain water accumulation in cytotoxic (cell swelling) edema, whereas it plays a major role in the clearance of excess brain water in vasogenic edema. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20517941" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#22" class="mim-tip-reference" title="Tait, M. J., Saadoun, S., Bell, B. A., Verkman, A. S., Papadopoulos, M. C. <strong>Increased brain edema in Aqp4-null mice in an experimental model of subarachnoid hemorrhage.</strong> Neuroscience 167: 60-67, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20132873/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20132873</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20132873[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.neuroscience.2010.01.053" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20132873">Tait et al. (2010)</a> studied the function of Aqp4 in a mouse model of subarachnoid hemorrhage in which a small amount of blood was injected into the basal cisterns. Aqp4-null mice developed significantly more brain swelling, brain water content, increased intracranial pressure, and worse neurologic function than wildtype mice. Although subarachnoid hemorrhage produced comparable increases in blood-brain barrier permeability in wildtype and Aqp4-null mice, mutant mice had a 2-fold reduction in glia limitans osmotic permeability. <a href="#22" class="mim-tip-reference" title="Tait, M. J., Saadoun, S., Bell, B. A., Verkman, A. S., Papadopoulos, M. C. <strong>Increased brain edema in Aqp4-null mice in an experimental model of subarachnoid hemorrhage.</strong> Neuroscience 167: 60-67, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20132873/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20132873</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20132873[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.neuroscience.2010.01.053" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20132873">Tait et al. (2010)</a> concluded that Aqp4-null mice manifested increased brain edema following subarachnoid hemorrhage as a consequence of reduced elimination of excess brain water. Together, these studies indicated that the role of Aqp4 is dependent on the type of injury. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20132873" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Sapkota, D., Florian, C., Doherty, B. M., White, K. M., Reardon, K. M., Ge, X., Garbow, J. R., Yuede, C. M., Cirrito, J. R., Dougherty, J. D. <strong>Aqp4 stop codon readthrough facilitates amyloid-beta clearance from the brain.</strong> Brain 145: 2982-2990, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36001414/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36001414</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=36001414[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/brain/awac199" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="36001414">Sapkota et al. (2022)</a> generated Aqp4X-specific knockout mice that lacked perivascular Aqp4X but retained expression of canonical Aqp4, with no significant change in total Aqp4 levels. Aqp4X-knockout brain was structurally normal with no apparent gliosis, and mutant mice had normal weight at weaning and were grossly indistinguishable from wildtype. However, Aqp4X-knockout mice displayed reduced A-beta (<a href="/entry/104760">104760</a>) clearance, leading to elevated brain interstitial fluid A-beta levels. Analysis of an aged Alzheimer disease (AD; <a href="/entry/104300">104300</a>) mouse model showed a decreased Aqp4X/Aqp4 ratio. Moreover, Aqp4X was not only required for efficient clearance of A-beta, but it was also relatively lost as disease progressed in AD mice. Using a high-throughput screen and counterscreen, the authors identified and validated apigenin and sulphaquinoxaline as compounds that enhanced readthrough expression of Aqp4X. Treatment of AD mice with these readthrough enhancers promoted a decrease of A-beta in an Aqp4X-dependent manner. In contrast, the readthrough enhancers lost their effect in Aqp4X-knockout mice, confirming that their ability to alter A-beta levels required Aqp4X. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36001414" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In 2 sibs (P4 and P5), born of consanguineous parents, with remitting megalencephalic leukoencephalopathy with subcortical cysts-4 (MLC4; <a href="/entry/620448">620448</a>), <a href="#17" class="mim-tip-reference" title="Passchier, E. M. J., Kerst, S., Brouwers, E., Hamilton, E. M. C., Bisseling, Q., Bugiani, M., Waisfisz, Q., Kitchen, P., Unger, L., Breur, M., Hoogterp, L., de Vries, S. I., and 12 others. <strong>Aquaporin-4 and GPRC5B: old and new players in controlling brain oedema.</strong> Brain 146: 3444-3454, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/37143309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">37143309</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=37143309[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/brain/awad146" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="37143309">Passchier et al. (2023)</a> identified a homozygous c.643G-A transition in the AQP4 gene, resulting in an ala215-to-thr (A215T) substitution at a highly conserved residue in the M7 loop in the second NPA motif that forms part of the channel pore. The mutation, which was found by a combination of homozygosity mapping and candidate gene sequencing, segregated with the disorder in the family. It was found in 4 of 251,462 alleles in gnomAD, only in the heterozygous state. Western blot analysis of MDCK cells transfected with the mutation showed no detectable expression of mutant AQP4, suggesting that the mutant protein is unstable and rapidly degraded. Functional studies showed no change in swelling and shrinking rate constants when the cells with the A215T mutation were exposed to hypotonic or hypertonic shock, whereas cells with wildtype AQP4 responded with increased swelling and shrinking under the same conditions. Overexpression of the A215T mutation in HEK293 cells showed detectable, but reduced, AQP4 membrane localization compared to controls. Mutant AQP4 formed large intracellular protein aggregates, and there was a 60% reduction in membrane localization compared to wildtype. Overexpression of mutant AQP4 increased swelling and shrinking in response to shock, but the rates were significantly reduced compared to wildtype. The findings suggested that mutant AQP4 reaching the cell membrane retains some residual water channel function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=37143309" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="#Jung1994" class="mim-tip-reference" title="Jung, J. S., Preston, G. M., Smith, B. L., Guggino, W. B., Agre, P. <strong>Molecular structure of the water channel through aquaporin CHIP: the hourglass model.</strong> J. Biol. Chem. 269: 14648-14654, 1994.">Jung et al. (1994)</a>
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<li>
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<a id="1" class="mim-anchor"></a>
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<a id="Amiry-Moghaddam2003" class="mim-anchor"></a>
|
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<div class="">
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Amiry-Moghaddam, M., Otsuka, T., Hurn, P. D., Traystman, R. J., Haug, F.-M., Froehner, S. C., Adams, M. E., Neely, J. D., Agre, P., Ottersen, O. P., Bhardwaj, A.
|
|
<strong>An alpha-syntrophin-dependent pool of AQP4 in astroglial end-feet confers bidirectional water flow between blood and brain.</strong>
|
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Proc. Nat. Acad. Sci. 100: 2106-2111, 2003.
|
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|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12578959/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12578959</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12578959" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.0437946100" target="_blank">Full Text</a>]
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<a id="Amiry-Moghaddam2003" class="mim-anchor"></a>
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Amiry-Moghaddam, M., Williamson, A., Palomba, M., Eid, T., de Lanerolle, N. C., Nagelhus, E. A., Adams, M. E., Froehner, S. C., Agre, P., Ottersen, O. P.
|
|
<strong>Delayed K(+) clearance associated with aquaporin-4 mislocalization: phenotypic defects in brains of alpha-syntrophin-null mice.</strong>
|
|
Proc. Nat. Acad. Sci. 100: 13615-13620, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14597704/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14597704</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14597704[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14597704" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.2336064100" target="_blank">Full Text</a>]
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</li>
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<a id="3" class="mim-anchor"></a>
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<a id="Eid2005" class="mim-anchor"></a>
|
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Eid, T., Lee, T.-S. W., Thomas, M. J., Amiry-Moghaddam, M., Bjornsen, L. P., Spencer, D. D., Agre, P., Ottersen, O. P., de Lanerolle, N. C.
|
|
<strong>Loss of perivascular aquaporin 4 may underlie deficient water and K(+) homeostasis in the human epileptogenic hippocampus.</strong>
|
|
Proc. Nat. Acad. Sci. 102: 1193-1198, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15657133/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15657133</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15657133[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15657133" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.0409308102" target="_blank">Full Text</a>]
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</li>
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<a id="4" class="mim-anchor"></a>
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<a id="Frigeri1998" class="mim-anchor"></a>
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Frigeri, A., Nicchia, G. P., Verbavatz, J. M., Valenti, G., Svelto, M.
|
|
<strong>Expression of aquaporin-4 in fast-twitch fibers of mammalian skeletal muscle.</strong>
|
|
J. Clin. Invest. 102: 695-703, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9710437/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9710437</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9710437" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1172/JCI2545" target="_blank">Full Text</a>]
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</li>
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<li>
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<a id="5" class="mim-anchor"></a>
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<a id="Jung1994" class="mim-anchor"></a>
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Jung, J. S., Bhat, R. V., Preston, G. M., Guggino, W. B., Baraban, J. M., Agre, P.
|
|
<strong>Molecular characterization of an aquaporin cDNA from brain: candidate osmoreceptor and regulator of water balance.</strong>
|
|
Proc. Nat. Acad. Sci. 91: 13052-13056, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7528931/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7528931</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7528931" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.91.26.13052" target="_blank">Full Text</a>]
|
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</p>
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</div>
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</li>
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<li>
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<a id="6" class="mim-anchor"></a>
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<a id="Jung1994" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Jung, J. S., Preston, G. M., Smith, B. L., Guggino, W. B., Agre, P.
|
|
<strong>Molecular structure of the water channel through aquaporin CHIP: the hourglass model.</strong>
|
|
J. Biol. Chem. 269: 14648-14654, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7514176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7514176</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7514176" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
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<a id="Kimura2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kimura, A., Hsu, M., Seldin, M., Verkman, A. S., Scharfman, H. E., Binder, D. K.
|
|
<strong>Protective role of aquaporin-4 water channels after contusion spinal cord injury.</strong>
|
|
Ann. Neurol. 67: 794-801, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20517941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20517941</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20517941" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ana.22023" target="_blank">Full Text</a>]
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</li>
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<li>
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<a id="8" class="mim-anchor"></a>
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<a id="Lanciotti2012" class="mim-anchor"></a>
|
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Lanciotti, A., Brignone, M. S., Molinari, P., Visentin, S., De Nuccio, C., Macchia, G., Aiello, C., Bertini, E., Aloisi, F., Petrucci, T. C., Ambrosini, E.
|
|
<strong>Megalencephalic leukoencephalopathy with subcortical cysts protein 1 functionally cooperates with the TRPV4 cation channel to activate the response of astrocytes to osmotic stress: dysregulation by pathological mutations.</strong>
|
|
Hum. Molec. Genet. 21: 2166-2180, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22328087/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22328087</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22328087" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/dds032" target="_blank">Full Text</a>]
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|
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Lennon, V. A., Kryzer, T. J., Pittock, S. J., Verkman, A. S., Hinson, S. R.
|
|
<strong>IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel.</strong>
|
|
J. Exp. Med. 202: 473-477, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16087714/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16087714</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16087714[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16087714" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1084/jem.20050304" target="_blank">Full Text</a>]
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|
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<a id="Li2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
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|
|
Li, J., Patil, R. V., Verkman, A. S.
|
|
<strong>Mildly abnormal retinal function in transgenic mice without Muller cell aquaporin-4 water channels.</strong>
|
|
Invest. Ophthal. Vis. Sci. 43: 573-579, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11818406/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11818406</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11818406" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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|
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|
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|
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Li, J., Verkman, A. S.
|
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<strong>Impaired hearing in mice lacking aquaporin-4 water channels.</strong>
|
|
J. Biol. Chem. 276: 31233-31237, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11406631/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11406631</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11406631" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.M104368200" target="_blank">Full Text</a>]
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|
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|
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Lu, M., Lee, M. D., Smith, B. L., Jung, J. S., Agre, P., Verdijk, M. A. J., Merkx, G., Rijss, J. P. L., Deen, P. M. T.
|
|
<strong>The human AQP4 gene: definition of the locus encoding two water channel polypeptides in brain.</strong>
|
|
Proc. Nat. Acad. Sci. 93: 10908-10912, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8855281/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8855281</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8855281" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1073/pnas.93.20.10908" target="_blank">Full Text</a>]
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|
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|
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|
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|
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|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ma, T., Yang, B., Verkman, A. S.
|
|
<strong>Gene structure, cDNA cloning, and expression of a mouse mercurial-insensitive water channel.</strong>
|
|
Genomics 33: 382-388, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8660998/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8660998</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8660998" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1006/geno.1996.0214" target="_blank">Full Text</a>]
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|
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|
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|
|
<a id="Manley2000" class="mim-anchor"></a>
|
|
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|
|
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|
|
Manley, G. T., Fujimura, M., Ma, T., Noshita, N., Filiz, F., Bollen, A. W., Chan, P., Verkman, A. S.
|
|
<strong>Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke.</strong>
|
|
Nature Med. 6: 159-163, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10655103/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10655103</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10655103" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/72256" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
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|
|
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|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="McKeon2008" class="mim-anchor"></a>
|
|
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|
|
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|
|
McKeon, A., Lennon, V. A., Lotze, T., Tenenbaum, S., Ness, J. M., Rensel, M., Kuntz, N. L., Fryer, J. P., Homburger, H., Hunter, J., Weinshenker, B. G., Krecke, K., Lucchinetti, C. F., Pittock, S. J.
|
|
<strong>CNS aquaporin-4 autoimmunity in children.</strong>
|
|
Neurology 71: 93-100, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18509092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18509092</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18509092" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/01.wnl.0000314832.24682.c6" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Mhatre2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
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|
|
Mhatre, A. N., Stern, R. E., Li, J., Lalwani, A. K.
|
|
<strong>Aquaporin 4 expression in the mammalian inner ear and its role in hearing.</strong>
|
|
Biochem. Biophys. Res. Commun. 297: 987-996, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12359252/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12359252</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12359252" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0006-291x(02)02296-9" target="_blank">Full Text</a>]
|
|
|
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|
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|
|
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|
|
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|
|
|
|
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|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Passchier2023" class="mim-anchor"></a>
|
|
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|
|
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|
|
Passchier, E. M. J., Kerst, S., Brouwers, E., Hamilton, E. M. C., Bisseling, Q., Bugiani, M., Waisfisz, Q., Kitchen, P., Unger, L., Breur, M., Hoogterp, L., de Vries, S. I., and 12 others.
|
|
<strong>Aquaporin-4 and GPRC5B: old and new players in controlling brain oedema.</strong>
|
|
Brain 146: 3444-3454, 2023.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/37143309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">37143309</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=37143309[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=37143309" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
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[<a href="https://doi.org/10.1093/brain/awad146" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
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|
|
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|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Pittock2006" class="mim-anchor"></a>
|
|
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|
|
<p class="mim-text-font">
|
|
Pittock, S. J., Weinshenker, B. G., Lucchinetti, C. F., Wingerchuk, D. M., Corboy, J. R., Lennon, V. A.
|
|
<strong>Neuromyelitis optica brain lesions localized at sites of high aquaporin 4 expression.</strong>
|
|
Arch. Neurol. 63: 964-968, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16831965/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16831965</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16831965" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1001/archneur.63.7.964" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Saadoun2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Saadoun, S., Bell, B. A., Verkman, A. S., Papadopoulos, M. C.
|
|
<strong>Greatly improved neurological outcome after spinal cord compression injury in AQP4-deficient mice.</strong>
|
|
Brain 131: 1087-1098, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18267965/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18267965</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18267965" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
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|
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[<a href="https://doi.org/10.1093/brain/awn014" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Sapkota2022" class="mim-anchor"></a>
|
|
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|
|
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|
|
Sapkota, D., Florian, C., Doherty, B. M., White, K. M., Reardon, K. M., Ge, X., Garbow, J. R., Yuede, C. M., Cirrito, J. R., Dougherty, J. D.
|
|
<strong>Aqp4 stop codon readthrough facilitates amyloid-beta clearance from the brain.</strong>
|
|
Brain 145: 2982-2990, 2022.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36001414/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36001414</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=36001414[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36001414" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
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|
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[<a href="https://doi.org/10.1093/brain/awac199" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
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|
|
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|
|
|
|
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|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Sepramaniam2010" class="mim-anchor"></a>
|
|
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|
|
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|
|
Sepramaniam, S., Armugam, A., Lim, K. Y., Karolina, D. S., Swaminathan, P., Tan, J. R., Jeyaseelan, K.
|
|
<strong>MicroRNA 320a functions as a novel endogenous modulator of aquaporins 1 and 4 as well as a potential therapeutic target in cerebral ischemia.</strong>
|
|
J. Biol. Chem. 285: 29223-29230, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20628061/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20628061</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20628061[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20628061" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
|
|
|
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[<a href="https://doi.org/10.1074/jbc.M110.144576" target="_blank">Full Text</a>]
|
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|
|
|
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|
|
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|
|
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|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
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|
|
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|
|
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|
|
Tait, M. J., Saadoun, S., Bell, B. A., Verkman, A. S., Papadopoulos, M. C.
|
|
<strong>Increased brain edema in Aqp4-null mice in an experimental model of subarachnoid hemorrhage.</strong>
|
|
Neuroscience 167: 60-67, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20132873/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20132873</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20132873[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20132873" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.neuroscience.2010.01.053" target="_blank">Full Text</a>]
|
|
|
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|
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|
|
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|
|
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|
|
|
|
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|
|
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|
|
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|
|
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|
|
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|
|
Turtzo, L. C., Lee, M. D., Lu, M., Smith, B. L., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., Agre, P.
|
|
<strong>Cloning and chromosomal localization of mouse aquaporin 4: exclusion of a candidate mutant phenotype, ataxia.</strong>
|
|
Genomics 41: 267-270, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9143504/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9143504</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9143504" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
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|
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|
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[<a href="https://doi.org/10.1006/geno.1997.4641" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
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|
|
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|
|
|
|
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|
|
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|
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|
|
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|
|
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|
Vajda, Z., Pedersen, M., Fuchtbauer, E.-M., Wertz, K., Stodkilde-Jorgensen, H., Sulyok, E., Doczi, T., Neely, J. D., Agre, P., Frokier, J., Nielsen, S.
|
|
<strong>Delayed onset of brain edema and mislocalization of aquaporin-4 in dystrophin-null transgenic mice.</strong>
|
|
Proc. Nat. Acad. Sci. 99: 13131-13136, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12232046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12232046</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12232046[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12232046" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
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[<a href="https://doi.org/10.1073/pnas.192457099" target="_blank">Full Text</a>]
|
|
|
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|
|
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|
|
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|
|
|
|
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|
|
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|
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|
|
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|
|
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|
|
Vajda, Z., Promeneur, D., Doczi, T., Sulyok, E., Frokiaer, J., Ottersen, O. P., Neilsen, S.
|
|
<strong>Increased aquaporin-4 immunoreactivity in rat brain in response to systemic hyponatremia.</strong>
|
|
Biochem. Biophys. Res. Commun. 270: 495-503, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10753653/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10753653</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10753653" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1006/bbrc.2000.2472" target="_blank">Full Text</a>]
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|
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|
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|
|
|
|
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|
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|
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|
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|
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Wakayama, Y., Jimi, T., Inoue, M., Kojima, H., Murahashi, M., Kumagai, T., Yamashita, S., Hara, H., Shibuya, S.
|
|
<strong>Reduced aquaporin 4 expression in the muscle plasma membrane of patients with Duchenne muscular dystrophy.</strong>
|
|
Arch. Neurol. 59: 431-437, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11890849/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11890849</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11890849" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1001/archneur.59.3.431" target="_blank">Full Text</a>]
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|
|
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|
|
|
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|
|
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|
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|
|
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|
|
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|
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Yang, B., Ma, T., Verkman, A. S.
|
|
<strong>cDNA cloning, gene organization, and chromosomal localization of a human mercurial insensitive water channel: evidence for distinct transcriptional units.</strong>
|
|
J. Biol. Chem. 270: 22907-22913, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7559426/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7559426</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7559426" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.270.39.22907" target="_blank">Full Text</a>]
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 07/19/2023
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<div class="row collapse" id="mimCollapseContributors">
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<span class="mim-text-font">
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Bao Lige - updated : 12/06/2022<br>Patricia A. Hartz - updated : 07/08/2013<br>Patricia A. Hartz - updated : 7/25/2011<br>Cassandra L. Kniffin - updated : 7/21/2011<br>Cassandra L. Kniffin - updated : 9/30/2008<br>Cassandra L. Kniffin - updated : 2/15/2007<br>Cassandra L. Kniffin - updated : 4/25/2006<br>Victor A. McKusick - updated : 7/16/2004<br>Victor A. McKusick - updated : 3/28/2003<br>Patricia A. Hartz - updated : 12/17/2002<br>Cassandra L. Kniffin - updated : 12/6/2002<br>Victor A. McKusick - updated : 11/15/2002<br>Jane Kelly - updated : 10/23/2002<br>Patricia A. Hartz - updated : 6/4/2002<br>Carol A. Bocchini - updated : 3/21/1999<br>Victor A. McKusick - updated : 10/8/1998<br>Alan F. Scott - edited : 1/22/1997<br>Alan F. Scott - updated : 5/22/1996
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Creation Date:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 1/12/1995
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alopez : 08/17/2023
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alopez : 07/19/2023<br>ckniffin : 07/19/2023<br>mgross : 12/06/2022<br>carol : 10/10/2016<br>mgross : 07/08/2013<br>alopez : 12/4/2012<br>mgross : 7/25/2011<br>wwang : 7/25/2011<br>ckniffin : 7/21/2011<br>wwang : 10/3/2008<br>ckniffin : 9/30/2008<br>wwang : 2/19/2007<br>ckniffin : 2/15/2007<br>wwang : 5/10/2006<br>ckniffin : 4/25/2006<br>terry : 4/4/2005<br>terry : 3/3/2005<br>tkritzer : 7/22/2004<br>terry : 7/16/2004<br>terry : 5/16/2003<br>cwells : 4/3/2003<br>terry : 3/28/2003<br>mgross : 12/18/2002<br>terry : 12/17/2002<br>carol : 12/16/2002<br>tkritzer : 12/13/2002<br>ckniffin : 12/11/2002<br>ckniffin : 12/6/2002<br>cwells : 11/18/2002<br>terry : 11/15/2002<br>cwells : 10/23/2002<br>cwells : 10/23/2002<br>tkritzer : 9/5/2002<br>carol : 6/4/2002<br>carol : 6/4/2002<br>terry : 3/22/1999<br>carol : 3/21/1999<br>carol : 10/13/1998<br>terry : 10/8/1998<br>dkim : 6/30/1998<br>terry : 6/3/1998<br>mark : 1/22/1997<br>mark : 1/22/1997<br>mark : 1/22/1997<br>jamie : 12/6/1996<br>terry : 12/3/1996<br>carol : 1/13/1995<br>carol : 1/12/1995
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<span class="mim-font">
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<strong>*</strong> 600308
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<h3>
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AQUAPORIN 4; AQP4
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<em>Alternative titles; symbols</em>
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MERCURIAL-INSENSITIVE WATER CHANNEL; MIWC
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<strong><em>HGNC Approved Gene Symbol: AQP4</em></strong>
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Cytogenetic location: 18q11.2
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Genomic coordinates <span class="small">(GRCh38)</span> : 18:26,852,038-26,865,803 </span>
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<span class="small">(from NCBI)</span>
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<strong>Gene-Phenotype Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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18q11.2
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<span class="mim-font">
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?Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting
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620448
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<span class="mim-font">
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Autosomal recessive
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<span class="mim-font">
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3
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<strong>TEXT</strong>
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<strong>Description</strong>
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<p>The aquaporins are a family of water-selective membrane channels found in animals, plants, and microorganisms. AQP4 is the predominant water channel in the brain and has an important role in brain water homeostasis. It is abundant in mammalian brain and is concentrated in astrocytic foot processes at the blood-brain barrier (Amiry-Moghaddam et al., 2003; Lennon et al., 2005). </p><p>See also aquaporin-1 (AQP1; 107776), also known as CHIP (for 'channel-forming integral membrane protein'), which was the first protein shown to function as a molecular water channel and is naturally expressed in mammalian red cells, renal proximal tubules, and other water-permeable epithelia. AQP1 is abundant in the choroid plexus. AQP2 (107777) is the vasopressin-regulated water channel in renal collecting ducts and is the site of mutations in some forms of nephrogenic diabetes insipidus. AQP3 (600170) is the water channel in basolateral membranes of renal medullary collecting ducts.</p>
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<strong>Cloning and Expression</strong>
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<p>By homology cloning, Jung et al. (1994) isolated an AQP4 cDNA from a rat brain cDNA library and established its function and distribution. Like AQP1, the deduced polypeptide has 6 putative transmembrane domains but lacks cysteines at the known mercurial-sensitive sites. Two initiation sites were identified encoding polypeptides of 301 and 323 amino acids; expression of each in Xenopus oocytes conferred a 20-fold increase in osmotic water permeability not blocked by 1 mM HgCl(2), even after substitution of cysteine at the predicted mercury-sensitive site. Northern blot analysis and RNase protection demonstrated the mRNA to be abundant in mature rat brain but only weakly detectable in eye, kidney, intestine, and lung. In situ hybridization of brain localized the mRNA to ependymal cells lining the aqueduct, glial cells forming the edge of the cerebral cortex and brainstem, vasopressin-secretory neurons in supraoptic and paraventricular nuclei of hypothalamus, and Purkinje cells of cerebellum. Its distinctive expression pattern implicated this fourth mammalian member of the aquaporin water channel family as the osmoreceptor that regulates body water balance and mediates water flow within the central nervous system. </p><p>Several mammalian water channels have been cloned, most of which are inhibited by mercurials. Yang et al. (1995) cloned 2 distinct human cDNAs encoding AQP4, which they called mercurial-insensitive water channel (MIWC), from a fetal brain cDNA library. The longest open reading frame encoded 301 amino acids with 94% identity to rat MIWC. Expression of MIWC cRNAs in Xenopus oocytes increased osmotic water permeability by 10- to 20-fold in a mercurial-insensitive manner. </p><p>Ma et al. (1996) cloned 3 mouse MIWC cDNAs from a brain library. The predicted proteins differed at their amino termini as a consequence of alternative splicing. The investigators also characterized the expression patterns of the transcripts and studied the expressed protein product by cRNA microinjection into Xenopus oocytes. </p><p>Sapkota et al. (2022) noted that readthrough of the stop codon of mouse Aqp4 produces an extended Aqp4 isoform, Aqp4X. Aqp4X is exclusively perivascular within astrocytic endfeet in mouse brain, whereas canonical Aqp4 localizes to parenchyma away from blood vessels. </p>
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<strong>Gene Structure</strong>
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<p>Analysis of MIWC genomic clones by Yang et al. (1995) indicated 2 distinct but overlapping transcription units from which multiple MIWC mRNAs are transcribed. Three introns were present. Genomic Southern blot analysis indicated the presence of a single MIWC gene. </p><p>Lu et al. (1996) reported the isolation and characterization of the human AQP4 cDNAs and genomic DNA. Similar to other aquaporins, the AQP4 gene is composed of 4 exons encoding 127, 55, 27, and 92 amino acids separated by introns of 0.8, 0.3, and 5.2 kb. Unlike other aquaporins, an alternative coding initiation sequence (designated exon 0) was located 2.7 kb upstream of exon 1. When spliced together, M1 and the subsequent 10 amino acids are encoded by exon 0; the next 11 amino acids and M23 are encoded by exon 1. </p>
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<strong>Mapping</strong>
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<p>By chromosome-specific PCR and in situ hybridization, Yang et al. (1995) localized the MIWC gene to chromosome 18q22. </p><p>By fluorescence in situ hybridization, Lu et al. (1996) determined that the AQP4 gene maps to 18q11.2-q12.1. By interspecific backcross analysis, Turtzo et al. (1997) mapped the mouse Aqp4 gene to the proximal region of chromosome 18. </p>
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<strong>Gene Function</strong>
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<p>Analyzing the expression of AQP4 in mammalian skeletal muscle, Frigeri et al. (1998) found that, in immunohistochemical experiments, affinity-purified AQP4 antibodies stained selectively the sarcolemma of fast-twitch fibers. By immunogold electron microscopy, little or no intracellular labeling was detected. Other experiments provided for the first time evidence for the expression of an aquaporin in skeletal muscle correlated to a specific fiber-type metabolism. Frigeri et al. (1998) analyzed AQP4 expression in skeletal muscle of mdx mice; immunofluorescence experiments showed a marked reduction of AQP4 expression, suggesting a critical role in the membrane alteration of Duchenne muscular dystrophy (DMD; 310200). </p><p>Wakayama et al. (2002) analyzed skeletal muscle samples from 6 patients with DMD and found markedly reduced AQP4 expression by immunohistochemical staining and markedly decreased levels of AQP4 mRNA as measured by RT-PCR, compared to controls. Genomic analysis of the AQP4 gene revealed no abnormalities. The authors concluded that the reduced mRNA was due to either decreased transcription or increased degradation of the message. </p><p>Immunocytochemistry revealed strong AQP4 water channel expression in Muller cells in mouse retina and in fibrous astrocytes in optic nerve. Li et al. (2002) compared electroretinograms and retinal morphology in wildtype mice and transgenic knockout mice with no Aqp4. Significantly reduced electroretinogram b-wave potentials were recorded in 10-month-old null mice with smaller changes in 1-month-old mice. Morphologic analysis of retina by light and electron microscopy showed no differences in retinal ultrastructure. That retinal function was mildly impaired in Aqp4-null mice suggested a role for Aqp4 in Muller cell fluid balance. The authors suggested that AQP4 expression in supportive cells in the nervous system facilitates neural signal transduction in nearby electrically excitable cells. </p><p>Manley et al. (2000) reported that AQP4 negatively influences the outcome of brain edema. Other studies also suggested that AQP4 contributes to the development of brain edema (Vajda et al., 2000). Vajda et al. (2002) performed studies in dystrophin (300377) null transgenic mice indicating that dystrophin is necessary for polarized distribution of AQP4 protein in brain where facilitated movements of water occur across the blood-brain barrier and cerebrospinal fluid-brain interface. The results predicted that interference with the subcellular localization of AQP4 may have therapeutic potential for delaying the onset of impending brain edema. </p><p>Recovery from neuronal activation requires rapid clearance of potassium ions and restoration of osmotic equilibrium. The predominant water channel protein in brain, AQP4, is concentrated in the astrocyte endfeet membranes adjacent to blood vessels in neocortex and cerebellum by association with alpha-syntrophin (SNTA1; 601017). Amiry-Moghaddam et al. (2003) used immunogold electron microscopy to compare hippocampus of wildtype and alpha-syntrophin-null mice. They found that less than 10% of Aqp4 immunogold labeling was retained in the perivascular astrocyte endfeet membranes of the null mice, whereas labeling of the inwardly rectifying potassium channel Kir4.1 (602208) was largely unchanged. Several other experiments, including the demonstration that the intensity of hyperthermia-induced epileptic seizures was increased in approximately half of the null mice, led Amiry-Moghaddam et al. (2003) to propose that water flux through perivascular AQP4 is needed to sustain efficient removal of potassium ions after neuronal activation. </p><p>Using quantitative immunogold electron microscopy, Eid et al. (2005) showed that the density of AQP4 along the perivascular membrane domain of astrocytes was decreased by an average of 44% in area CA1 of hippocampi from 24 patients with mesial temporal lobe epilepsy with hippocampal sclerosis compared to controls. There was no difference in AQP4 density on the astrocyte membrane facing the neuropil. Further studies suggested that the loss of AQP4 was due to disruption of the dystrophin complex. Western blot analysis showed a significant increase in overall AQP4 in mesial temporal lobe epilepsy tissue compared to controls, consistent with the proliferation of astrocytes typical of hippocampal sclerosis. Eid et al. (2005) postulated that the loss of perivascular AQP4 in mesial temporal lobe epilepsy results in a perturbed flux of water through astrocytes, leading to impaired buffering of extracellular potassium and an increased propensity for seizures. </p><p>Lennon et al. (2005) found that a serum IgG autoantibody specific for neuromyelitis optica (NMO) binds selectively to the AQP4 channel. NMO is an inflammatory demyelinating disease that selectively affects optic nerves and spinal cord and is considered a severe variant of multiple sclerosis (MS; 126200), although the prognosis and treatment differ from MS. In 8 patients with NMO who were seropositive for NMO-IgG autoantibodies, Pittock et al. (2006) observed recurring and distinctive brain MRI abnormalities in hypothalamic and periventricular areas that corresponded to brain regions of high AQP4 expression. The findings further supported the hypothesis that AQP4-IgG plays a pathogenic role in NMO. </p><p>McKeon et al. (2008) identified 88 consecutive children who were NMO-IgG seropositive; clinical information was available for 58. The median age at symptom onset was 12 years (range, 4 to 18). Fifty-seven (98%) had attacks of either optic neuritis (83%) or transverse myelitis (78%), or both. Twenty-six (45%) had episodic cerebral symptoms, including encephalopathy, ophthalmoparesis, ataxia, seizures, intractable vomiting, or hiccups. Thirty-eight (68%) had brain MRI abnormalities, predominantly involving periventricular areas, but including other areas as well. Additional autoantibodies were detected in 57 (76%) of 75 patients, and 16 (42%) of 38 had a coexisting autoimmune disorder. Attacks were recurrent in 54 patients at 12 months follow-up. McKeon et al. (2008) concluded that AQP4 autoimmunity is a distinctive recurrent and widespread inflammatory CNS disease in children. </p><p>AQP1 and AQP4 regulate the movement of water in ischemic brain, and they appear to play a role in cerebral edema. By searching a microRNA (miRNA) database for miRNAs that could target the 3-prime UTRs of AQP1 and AQP4, Sepramaniam et al. (2010) identified MIR320A (614112). Knockdown of MIR320A via anti-MIR320A in a human astrocytoma cell line upregulated expression of AQP1 and AQP4 mRNA and protein. Conversely, overexpression of pre-MIR320A reduced expression of AQP1 and AQP4 mRNA and protein. Reporter gene assays confirmed direct targeting of the 3-prime UTRs of AQP1 and AQP4 by MIR320A. Astrocytes subjected to oxygen and glucose deprivation, which mimics the ischemic environment, downregulated expression of MIR320A, concomitant with upregulated expression of AQP1 and AQP4. Administration of anti-MIR320A to rats following occlusion of the middle cerebral artery reduced the infarct volume, whereas pre-MIR320A caused a further increase in infarct volume. Sepramaniam et al. (2010) concluded that MIR320 modulates AQP1 and AQP2 and may have a role in cerebral ischemia. </p><p>Using various methods, Lanciotti et al. (2012) found that MLC1 (605908), TRPV4 (605427), HEPACAM (611642), syntrophin, caveolin-1 (CAV1; 601047), Kir4.1, and AQP4 assembled into an Na,K-ATPase-associated multiprotein complex. In rat and human astrocyte cell lines, this Na,K-ATPase complex mediated swelling-induced cytosolic calcium increase and volume recovery in response to hyposmotic stress. MLC1 associated directly with the Na,K-ATPase beta-1 subunit (ATP1B1; 182330), and plasma membrane expression of MLC1 was required for assembly of the Na,K-ATPase complex. TRPV4 was required for calcium influx, and AQP4 was recruited to the complex following hyposmotic stress. </p>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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<p>In 2 sibs (P4 and P5), born of consanguineous parents, with remitting megalencephalic leukoencephalopathy with subcortical cysts-4 (MLC4; 620448), Passchier et al. (2023) identified a homozygous missense mutation in the AQP4 gene (A215T; 600308.0001) affecting the second NPA motif that forms part of the channel pore. The mutation, which was found by a combination of homozygosity mapping and candidate gene sequencing, segregated with the disorder in the family. Western blot analysis of MDCK cells transfected with the mutation showed no detectable expression of mutant AQP4, suggesting that the mutant protein is unstable and rapidly degraded. Functional studies showed no change in swelling and shrinking rate constants when the cells with the A215T mutation were exposed to hypotonic or hypertonic shock, whereas cells with wildtype AQP4 responded with increased swelling and shrinking under the same conditions. Overexpression of the A215T mutation in HEK293 cells showed detectable, but reduced, AQP4 membrane localization compared to controls. Mutant AQP4 formed large intracellular protein aggregates, and there was a 60% reduction in membrane localization compared to wildtype. Overexpression of mutant AQP4 increased swelling and shrinking in response to shock, but the rates were significantly reduced compared to wildtype. The findings suggested that mutant A215T AQP4 reaching the cell membrane retains some residual water channel function. </p>
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<p>Li and Verkman (2001) noted that several of the aquaporins localize in the mammalian inner ear and are proposed to play a role in hearing. They localized mouse Aqp1 in fibrocytes in the spiral ligament and Aqp4 in supporting epithelial cells in the organ of Corti. Li and Verkman (2001) developed aquaporin-null mice, targeting Aqp1, Aqp3, Aqp4, and Aqp5 (600442). They found that the threshold auditory brainstem response to a click stimulus was significantly increased in Aqp4-null mice. The hearing impairment in these mice was frequency independent and was not accompanied by anatomical abnormalities. They found no hearing impairment in any of the other aquaporin-null mice. By immunolocalization studies in mouse retina, Li et al. (2002) localized Aqp4 in Muller cells of the retina and in fibrous astrocytes of the optic nerve. Aqp4-null mice showed no difference in retinal ultrastructure, but electroretinograms of Aqp4-null mice indicated mildly impaired retinal function. </p><p>By immunolocalization of Aqp4 in mouse and rat inner ear, Mhatre et al. (2002) found that Aqp4 is expressed within the epithelia surrounding sensory cells of the auditory and vestibular sensory organs and in glial cells surrounding the auditory nerve. Aqp4 knockout mice demonstrated impaired hearing. Neural conduction times in knockout mice were normal, suggesting that cochlear dysfunction was the cause of hearing impairment. </p><p>AQP4 is anchored at the perivascular and subpial membranes by its C terminus to alpha-syntrophin (SNTA1; 601017), an adaptor protein associated with dystrophin. To test functions of the perivascular AQP4 pool, Amiry-Moghaddam et al. (2003) studied mice homozygous for targeted disruption of SNTA1. These animals showed a marked loss of Aqp4 from perivascular and subpial membranes but no decrease in other membrane domains, as judged by quantitative immunogold electron microscopy. In the basal state, perivascular and subpial astroglial endfeet were swollen in brains of SNTA1 -/- mice compared to wildtype mice, suggesting reduced clearance of water generated by brain metabolism. When stressed by transient cerebral ischemia, brain edema was attenuated in these same null mice, indicative of reduced water influx. These studies identified a specific, syntrophin-dependent AQP4 pool that is expressed at distinct membrane domains and mediates bidirectional transport of water across the brain-blood interface. The anchoring of AQP4 to SNTA1 may be a target for treatment of brain edema, but therapeutic manipulations of AQP4 must consider the bidirectional water flux through this molecule. </p><p>Compression spinal cord injury, caused by bilateral constant pressure, is thought to cause mechanical disruption of cells and ischemia and is a model of cytotoxic edema. In contrast, contusion spinal cord injury, caused by impact, causes disruption of blood vessels and is a model of vasogenic edema. Saadoun et al. (2008) found that Aqp4-null mice had greatly improved neurologic outcome after spinal cord compression injury compared to wildtype mice. Aqp4-null mice had less hindlimb weakness, better motor and sensory indices, and less neuronal death, myelin vacuolation, and swelling and pressure in the spinal cord compared to wildtype mice. In wildtype mice, Aqp4 immunoreactivity at the injury site was increased in gray and white matter at 48 hours. The findings suggested that Aqp4 provides a major route for excess water entry into the injured spinal cord after compression injury, which in turn causes spinal cord swelling, edema, elevated spinal cord pressure, and neurologic impairment. Saadoun et al. (2008) suggested that inhibition or downregulation of Aqp4 could be an early neuroprotective maneuver in compression spinal cord injury by reducing cytotoxic edema. </p><p>In contrast, Kimura et al. (2010) found that Aqp4-null mice had more functional deterioration after contusion spinal cord injury than wildtype mice. Aqp4-null mice had worse motor recovery, prolonged bladder dysfunction, and greater lesion volume, neuronal loss, cyst formation, and edema in the spinal cord compared to wildtype mice after contusion spinal cord injury. The results suggested that Aqp4 plays a protective role after contusion spinal cord injury by facilitating the clearance of excess tissue water. The studies highlighted the bidirectional role of AQP4 in the brain: AQP4 is a major route for brain water accumulation in cytotoxic (cell swelling) edema, whereas it plays a major role in the clearance of excess brain water in vasogenic edema. </p><p>Tait et al. (2010) studied the function of Aqp4 in a mouse model of subarachnoid hemorrhage in which a small amount of blood was injected into the basal cisterns. Aqp4-null mice developed significantly more brain swelling, brain water content, increased intracranial pressure, and worse neurologic function than wildtype mice. Although subarachnoid hemorrhage produced comparable increases in blood-brain barrier permeability in wildtype and Aqp4-null mice, mutant mice had a 2-fold reduction in glia limitans osmotic permeability. Tait et al. (2010) concluded that Aqp4-null mice manifested increased brain edema following subarachnoid hemorrhage as a consequence of reduced elimination of excess brain water. Together, these studies indicated that the role of Aqp4 is dependent on the type of injury. </p><p>Sapkota et al. (2022) generated Aqp4X-specific knockout mice that lacked perivascular Aqp4X but retained expression of canonical Aqp4, with no significant change in total Aqp4 levels. Aqp4X-knockout brain was structurally normal with no apparent gliosis, and mutant mice had normal weight at weaning and were grossly indistinguishable from wildtype. However, Aqp4X-knockout mice displayed reduced A-beta (104760) clearance, leading to elevated brain interstitial fluid A-beta levels. Analysis of an aged Alzheimer disease (AD; 104300) mouse model showed a decreased Aqp4X/Aqp4 ratio. Moreover, Aqp4X was not only required for efficient clearance of A-beta, but it was also relatively lost as disease progressed in AD mice. Using a high-throughput screen and counterscreen, the authors identified and validated apigenin and sulphaquinoxaline as compounds that enhanced readthrough expression of Aqp4X. Treatment of AD mice with these readthrough enhancers promoted a decrease of A-beta in an Aqp4X-dependent manner. In contrast, the readthrough enhancers lost their effect in Aqp4X-knockout mice, confirming that their ability to alter A-beta levels required Aqp4X. </p>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>1 Selected Example):</strong>
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<h4>
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<span class="mim-font">
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<strong>.0001 MEGALENCEPHALIC LEUKOENCEPHALOPATHY WITH SUBCORTICAL CYSTS 4, REMITTING (1 family)</strong>
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AQP4, ALA215THR ({dbSNP rs148498248})
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<br />
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SNP: rs148498248,
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gnomAD: rs148498248,
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ClinVar: RCV003315379
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<p>In 2 sibs (P4 and P5), born of consanguineous parents, with remitting megalencephalic leukoencephalopathy with subcortical cysts-4 (MLC4; 620448), Passchier et al. (2023) identified a homozygous c.643G-A transition in the AQP4 gene, resulting in an ala215-to-thr (A215T) substitution at a highly conserved residue in the M7 loop in the second NPA motif that forms part of the channel pore. The mutation, which was found by a combination of homozygosity mapping and candidate gene sequencing, segregated with the disorder in the family. It was found in 4 of 251,462 alleles in gnomAD, only in the heterozygous state. Western blot analysis of MDCK cells transfected with the mutation showed no detectable expression of mutant AQP4, suggesting that the mutant protein is unstable and rapidly degraded. Functional studies showed no change in swelling and shrinking rate constants when the cells with the A215T mutation were exposed to hypotonic or hypertonic shock, whereas cells with wildtype AQP4 responded with increased swelling and shrinking under the same conditions. Overexpression of the A215T mutation in HEK293 cells showed detectable, but reduced, AQP4 membrane localization compared to controls. Mutant AQP4 formed large intracellular protein aggregates, and there was a 60% reduction in membrane localization compared to wildtype. Overexpression of mutant AQP4 increased swelling and shrinking in response to shock, but the rates were significantly reduced compared to wildtype. The findings suggested that mutant AQP4 reaching the cell membrane retains some residual water channel function. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>See Also:</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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Jung et al. (1994)
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</span>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<ol>
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<li>
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<p class="mim-text-font">
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Amiry-Moghaddam, M., Otsuka, T., Hurn, P. D., Traystman, R. J., Haug, F.-M., Froehner, S. C., Adams, M. E., Neely, J. D., Agre, P., Ottersen, O. P., Bhardwaj, A.
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<strong>An alpha-syntrophin-dependent pool of AQP4 in astroglial end-feet confers bidirectional water flow between blood and brain.</strong>
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Proc. Nat. Acad. Sci. 100: 2106-2111, 2003.
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[PubMed: 12578959]
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[Full Text: https://doi.org/10.1073/pnas.0437946100]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Amiry-Moghaddam, M., Williamson, A., Palomba, M., Eid, T., de Lanerolle, N. C., Nagelhus, E. A., Adams, M. E., Froehner, S. C., Agre, P., Ottersen, O. P.
|
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<strong>Delayed K(+) clearance associated with aquaporin-4 mislocalization: phenotypic defects in brains of alpha-syntrophin-null mice.</strong>
|
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Proc. Nat. Acad. Sci. 100: 13615-13620, 2003.
|
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[PubMed: 14597704]
|
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|
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[Full Text: https://doi.org/10.1073/pnas.2336064100]
|
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Eid, T., Lee, T.-S. W., Thomas, M. J., Amiry-Moghaddam, M., Bjornsen, L. P., Spencer, D. D., Agre, P., Ottersen, O. P., de Lanerolle, N. C.
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<strong>Loss of perivascular aquaporin 4 may underlie deficient water and K(+) homeostasis in the human epileptogenic hippocampus.</strong>
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|
Proc. Nat. Acad. Sci. 102: 1193-1198, 2005.
|
|
|
|
|
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[PubMed: 15657133]
|
|
|
|
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[Full Text: https://doi.org/10.1073/pnas.0409308102]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Frigeri, A., Nicchia, G. P., Verbavatz, J. M., Valenti, G., Svelto, M.
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<strong>Expression of aquaporin-4 in fast-twitch fibers of mammalian skeletal muscle.</strong>
|
|
J. Clin. Invest. 102: 695-703, 1998.
|
|
|
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|
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[PubMed: 9710437]
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|
|
|
|
[Full Text: https://doi.org/10.1172/JCI2545]
|
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</p>
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</li>
|
|
|
|
<li>
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|
<p class="mim-text-font">
|
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Jung, J. S., Bhat, R. V., Preston, G. M., Guggino, W. B., Baraban, J. M., Agre, P.
|
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<strong>Molecular characterization of an aquaporin cDNA from brain: candidate osmoreceptor and regulator of water balance.</strong>
|
|
Proc. Nat. Acad. Sci. 91: 13052-13056, 1994.
|
|
|
|
|
|
[PubMed: 7528931]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.91.26.13052]
|
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|
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</p>
|
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</li>
|
|
|
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<li>
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<p class="mim-text-font">
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Jung, J. S., Preston, G. M., Smith, B. L., Guggino, W. B., Agre, P.
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<strong>Molecular structure of the water channel through aquaporin CHIP: the hourglass model.</strong>
|
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J. Biol. Chem. 269: 14648-14654, 1994.
|
|
|
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|
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[PubMed: 7514176]
|
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|
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|
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
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Kimura, A., Hsu, M., Seldin, M., Verkman, A. S., Scharfman, H. E., Binder, D. K.
|
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<strong>Protective role of aquaporin-4 water channels after contusion spinal cord injury.</strong>
|
|
Ann. Neurol. 67: 794-801, 2010.
|
|
|
|
|
|
[PubMed: 20517941]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.22023]
|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lanciotti, A., Brignone, M. S., Molinari, P., Visentin, S., De Nuccio, C., Macchia, G., Aiello, C., Bertini, E., Aloisi, F., Petrucci, T. C., Ambrosini, E.
|
|
<strong>Megalencephalic leukoencephalopathy with subcortical cysts protein 1 functionally cooperates with the TRPV4 cation channel to activate the response of astrocytes to osmotic stress: dysregulation by pathological mutations.</strong>
|
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Hum. Molec. Genet. 21: 2166-2180, 2012.
|
|
|
|
|
|
[PubMed: 22328087]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/dds032]
|
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</p>
|
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</li>
|
|
|
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<li>
|
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<p class="mim-text-font">
|
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Lennon, V. A., Kryzer, T. J., Pittock, S. J., Verkman, A. S., Hinson, S. R.
|
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<strong>IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel.</strong>
|
|
J. Exp. Med. 202: 473-477, 2005.
|
|
|
|
|
|
[PubMed: 16087714]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1084/jem.20050304]
|
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</p>
|
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</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
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Li, J., Patil, R. V., Verkman, A. S.
|
|
<strong>Mildly abnormal retinal function in transgenic mice without Muller cell aquaporin-4 water channels.</strong>
|
|
Invest. Ophthal. Vis. Sci. 43: 573-579, 2002.
|
|
|
|
|
|
[PubMed: 11818406]
|
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|
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|
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|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Li, J., Verkman, A. S.
|
|
<strong>Impaired hearing in mice lacking aquaporin-4 water channels.</strong>
|
|
J. Biol. Chem. 276: 31233-31237, 2001.
|
|
|
|
|
|
[PubMed: 11406631]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M104368200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lu, M., Lee, M. D., Smith, B. L., Jung, J. S., Agre, P., Verdijk, M. A. J., Merkx, G., Rijss, J. P. L., Deen, P. M. T.
|
|
<strong>The human AQP4 gene: definition of the locus encoding two water channel polypeptides in brain.</strong>
|
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Proc. Nat. Acad. Sci. 93: 10908-10912, 1996.
|
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|
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|
[PubMed: 8855281]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.93.20.10908]
|
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|
|
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|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ma, T., Yang, B., Verkman, A. S.
|
|
<strong>Gene structure, cDNA cloning, and expression of a mouse mercurial-insensitive water channel.</strong>
|
|
Genomics 33: 382-388, 1996.
|
|
|
|
|
|
[PubMed: 8660998]
|
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|
|
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[Full Text: https://doi.org/10.1006/geno.1996.0214]
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</p>
|
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</li>
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<li>
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<p class="mim-text-font">
|
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Manley, G. T., Fujimura, M., Ma, T., Noshita, N., Filiz, F., Bollen, A. W., Chan, P., Verkman, A. S.
|
|
<strong>Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke.</strong>
|
|
Nature Med. 6: 159-163, 2000.
|
|
|
|
|
|
[PubMed: 10655103]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/72256]
|
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</p>
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|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
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McKeon, A., Lennon, V. A., Lotze, T., Tenenbaum, S., Ness, J. M., Rensel, M., Kuntz, N. L., Fryer, J. P., Homburger, H., Hunter, J., Weinshenker, B. G., Krecke, K., Lucchinetti, C. F., Pittock, S. J.
|
|
<strong>CNS aquaporin-4 autoimmunity in children.</strong>
|
|
Neurology 71: 93-100, 2008.
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|
|
|
|
|
[PubMed: 18509092]
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[Full Text: https://doi.org/10.1212/01.wnl.0000314832.24682.c6]
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</p>
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</li>
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|
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<li>
|
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<p class="mim-text-font">
|
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Mhatre, A. N., Stern, R. E., Li, J., Lalwani, A. K.
|
|
<strong>Aquaporin 4 expression in the mammalian inner ear and its role in hearing.</strong>
|
|
Biochem. Biophys. Res. Commun. 297: 987-996, 2002.
|
|
|
|
|
|
[PubMed: 12359252]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0006-291x(02)02296-9]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Passchier, E. M. J., Kerst, S., Brouwers, E., Hamilton, E. M. C., Bisseling, Q., Bugiani, M., Waisfisz, Q., Kitchen, P., Unger, L., Breur, M., Hoogterp, L., de Vries, S. I., and 12 others.
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<strong>Aquaporin-4 and GPRC5B: old and new players in controlling brain oedema.</strong>
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Brain 146: 3444-3454, 2023.
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[PubMed: 37143309]
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[Full Text: https://doi.org/10.1093/brain/awad146]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Pittock, S. J., Weinshenker, B. G., Lucchinetti, C. F., Wingerchuk, D. M., Corboy, J. R., Lennon, V. A.
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<strong>Neuromyelitis optica brain lesions localized at sites of high aquaporin 4 expression.</strong>
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Arch. Neurol. 63: 964-968, 2006.
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[PubMed: 16831965]
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[Full Text: https://doi.org/10.1001/archneur.63.7.964]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Saadoun, S., Bell, B. A., Verkman, A. S., Papadopoulos, M. C.
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<strong>Greatly improved neurological outcome after spinal cord compression injury in AQP4-deficient mice.</strong>
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Brain 131: 1087-1098, 2008.
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[PubMed: 18267965]
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[Full Text: https://doi.org/10.1093/brain/awn014]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Sapkota, D., Florian, C., Doherty, B. M., White, K. M., Reardon, K. M., Ge, X., Garbow, J. R., Yuede, C. M., Cirrito, J. R., Dougherty, J. D.
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<strong>Aqp4 stop codon readthrough facilitates amyloid-beta clearance from the brain.</strong>
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Brain 145: 2982-2990, 2022.
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[PubMed: 36001414]
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[Full Text: https://doi.org/10.1093/brain/awac199]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Sepramaniam, S., Armugam, A., Lim, K. Y., Karolina, D. S., Swaminathan, P., Tan, J. R., Jeyaseelan, K.
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<strong>MicroRNA 320a functions as a novel endogenous modulator of aquaporins 1 and 4 as well as a potential therapeutic target in cerebral ischemia.</strong>
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J. Biol. Chem. 285: 29223-29230, 2010.
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[PubMed: 20628061]
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|
[Full Text: https://doi.org/10.1074/jbc.M110.144576]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tait, M. J., Saadoun, S., Bell, B. A., Verkman, A. S., Papadopoulos, M. C.
|
|
<strong>Increased brain edema in Aqp4-null mice in an experimental model of subarachnoid hemorrhage.</strong>
|
|
Neuroscience 167: 60-67, 2010.
|
|
|
|
|
|
[PubMed: 20132873]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.neuroscience.2010.01.053]
|
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|
|
|
|
</p>
|
|
</li>
|
|
|
|
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|
|
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|
|
Turtzo, L. C., Lee, M. D., Lu, M., Smith, B. L., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., Agre, P.
|
|
<strong>Cloning and chromosomal localization of mouse aquaporin 4: exclusion of a candidate mutant phenotype, ataxia.</strong>
|
|
Genomics 41: 267-270, 1997.
|
|
|
|
|
|
[PubMed: 9143504]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1997.4641]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
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|
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Vajda, Z., Pedersen, M., Fuchtbauer, E.-M., Wertz, K., Stodkilde-Jorgensen, H., Sulyok, E., Doczi, T., Neely, J. D., Agre, P., Frokier, J., Nielsen, S.
|
|
<strong>Delayed onset of brain edema and mislocalization of aquaporin-4 in dystrophin-null transgenic mice.</strong>
|
|
Proc. Nat. Acad. Sci. 99: 13131-13136, 2002.
|
|
|
|
|
|
[PubMed: 12232046]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.192457099]
|
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|
|
|
|
</p>
|
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</li>
|
|
|
|
<li>
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<p class="mim-text-font">
|
|
Vajda, Z., Promeneur, D., Doczi, T., Sulyok, E., Frokiaer, J., Ottersen, O. P., Neilsen, S.
|
|
<strong>Increased aquaporin-4 immunoreactivity in rat brain in response to systemic hyponatremia.</strong>
|
|
Biochem. Biophys. Res. Commun. 270: 495-503, 2000.
|
|
|
|
|
|
[PubMed: 10753653]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/bbrc.2000.2472]
|
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</p>
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</li>
|
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|
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<li>
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Wakayama, Y., Jimi, T., Inoue, M., Kojima, H., Murahashi, M., Kumagai, T., Yamashita, S., Hara, H., Shibuya, S.
|
|
<strong>Reduced aquaporin 4 expression in the muscle plasma membrane of patients with Duchenne muscular dystrophy.</strong>
|
|
Arch. Neurol. 59: 431-437, 2002.
|
|
|
|
|
|
[PubMed: 11890849]
|
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|
|
|
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[Full Text: https://doi.org/10.1001/archneur.59.3.431]
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</li>
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Yang, B., Ma, T., Verkman, A. S.
|
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<strong>cDNA cloning, gene organization, and chromosomal localization of a human mercurial insensitive water channel: evidence for distinct transcriptional units.</strong>
|
|
J. Biol. Chem. 270: 22907-22913, 1995.
|
|
|
|
|
|
[PubMed: 7559426]
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[Full Text: https://doi.org/10.1074/jbc.270.39.22907]
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