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<div class="action-panel-control-wrap">
<label for="email-to" class="action-panel-label required-field-asterisk">
To:
</label>
<input type="email" aria-label="Recipient Email Address" placeholder="email@example.com" id="email-to" class="email-to" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="100" required>
</div>
<div class="action-panel-control-wrap">
<label for="email-from" class="action-panel-label">
From:
</label>
<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256">
</div>
<div class="action-panel-control-wrap">
<label for="email-citation-format" class="action-panel-label">
Format:
</label>
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
<option selected="selected" value="summary">Summary</option>
<option value="summary-text">Summary (text)</option>
<option value="abstract">Abstract</option>
<option value="abstract-text">Abstract (text)</option>
</select>
</div>
<div class="include-supplemental-container">
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
</div>
<div class="form-field recaptcha ">
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
</div>
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="send">
Send email
</button>
<button class="action-panel-cancel"
aria-label="Close 'Email citations' panel"
ref="linksrc=close_email_panel"
aria-controls="email-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="cancel">
Cancel
</button>
</div>
<input type="hidden" name="email-search-details" value="" />
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
</form>
</div>
</div>
<div id="collections-action-panel"
class="collections-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-collections-open-panel-enabled="false"
data-collections-open-panel-url-hash="#open-collections-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to Collections
</h3>
<form id="collections-action-panel-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-myncbi-max-collection-name-length="100"
data-add-to-collection-max-amount="1000"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
<input type="hidden" name="csrfmiddlewaretoken" value="F4UVkTya1sspKg7jkjMUcrhertQ1YorRWRE0XJ1wB3fTEHd9XCpWGzNSZxydRZZb">
<div class="choice-group" role="radiogroup">
<ul class="radio-group-items">
<li>
<input type="radio"
id="collections-action-panel-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_new">
<label for="collections-action-panel-new">Create a new collection</label>
</li>
<li>
<input type="radio"
id="collections-action-panel-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_existing">
<label for="collections-action-panel-existing">Add to an existing collection</label>
</li>
</ul>
</div>
<div class="controls-wrapper">
<div class="action-panel-control-wrap new-collections-controls">
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label>
<input
type="text"
name="add-to-new-collection"
id="collections-action-panel-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="save_share"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection">
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div>
</div>
<div class="action-panel-control-wrap existing-collections-controls">
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
Choose a collection:
</label>
<select id="collections-action-panel-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="save_share"
data-ga-action="select_collection"
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
</select>
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br>
<a href="#">Please try again</a>
</div>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="add">
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to Collections' panel"
ref="linksrc=close_collections_panel"
aria-controls="collections-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="bibliography-action-panel"
class="bibliography-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-bibliography-open-panel-enabled="false"
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to My Bibliography
</h3>
<form id="bibliography-action-panel-form"
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-add-to-bibliography-max-amount="100"
data-add-to-bibliography-batch-size="10"
data-bibliography-delegates-url="/list-bibliography-delegates/"
data-add-to-bibliography-url="/add-to-bibliography/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
<input type="hidden" name="csrfmiddlewaretoken" value="F4UVkTya1sspKg7jkjMUcrhertQ1YorRWRE0XJ1wB3fTEHd9XCpWGzNSZxydRZZb">
<div class="action-panel-control-wrap bibliographies-controls">
<div class="choice-group">
<ul class="bibliographies-action-add radio-group-items">
<li>
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
<label for="my-bibliography">My Bibliography</label>
</li>
</ul>
</div>
</div>
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your delegates due to an error<br>
<a href="#">Please try again</a>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore>
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to bibliography' panel"
ref="linksrc=close_bibliography_panel"
aria-controls="bibliography-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="mybib"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
data-saved-search-open-panel-enabled="false"
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your saved search
</h2>
<form id="saved-search-action-panel-form"
class="saved-search-action-panel-form action-panel-content action-form"
data-create-saved-search-url="/create-saved-search/"
data-try-search-terms-url="/try-search-term/"
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
<input type="hidden" name="csrfmiddlewaretoken" value="F4UVkTya1sspKg7jkjMUcrhertQ1YorRWRE0XJ1wB3fTEHd9XCpWGzNSZxydRZZb">
<div class="action-panel-control-wrap">
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
Name of saved search:
</label>
<input maxlength="200"
type="text"
name="saved-search-name"
id="saved-search-name"
class="saved-search-name"
value=""
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
Search terms:
</label>
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
</div>
<div class="test-search-term-wrap">
<a href="#" class="try-search-term">Test search terms</a>
</div>
<div class="choice-group action-panel-extra-margin-top">
<span class="action-panel-label" id="fieldset-label">
Would you like email updates of new search results?
</span>
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
<ul class="radio-group-items">
<li>
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
</li>
<li>
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
<label for="saved-search-alert-no" class="action-panel-label">No</label>
</li>
</ul>
</fieldset>
</div>
<div class="alert-schedule-wrap">
<div class="action-panel-control-wrap">
<label class="action-panel-label">
Email:
</label>
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
</div>
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="saved-search-frequency" class="action-panel-label">
Frequency:
</label>
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
<option value="monthly">Monthly</option>
<option value="weekly">Weekly</option>
<option value="daily">Daily</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-monthly-additional">
<label for="saved-search-monthly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
<option value="Sunday">The first Sunday</option>
<option value="Monday">The first Monday</option>
<option value="Tuesday">The first Tuesday</option>
<option value="Wednesday">The first Wednesday</option>
<option value="Thursday">The first Thursday</option>
<option value="Friday">The first Friday</option>
<option value="Saturday">The first Saturday</option>
<option value="day">The first day</option>
<option value="weekday">The first weekday</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-weekly-additional">
<label for="saved-search-weekly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
<option value="Sunday">Sunday</option>
<option value="Monday">Monday</option>
<option value="Tuesday">Tuesday</option>
<option value="Wednesday">Wednesday</option>
<option value="Thursday">Thursday</option>
<option value="Friday">Friday</option>
<option value="Saturday">Saturday</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-report" class="action-panel-label">
Report format:
</label>
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
<option value="DocSum">Summary</option>
<option value="DocSumText">Summary (text)</option>
<option value="Abstract">Abstract</option>
<option value="AbstractText">Abstract (text)</option>
<option value="MEDLINE">PubMed</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-amount" class="action-panel-label">
Send at most:
</label>
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
<option value="1">1 item</option>
<option value="5" selected>5 items</option>
<option value="10">10 items</option>
<option value="20">20 items</option>
<option value="50">50 items</option>
<option value="100">100 items</option>
<option value="200">200 items</option>
</select>
</div>
<div>
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
Send even when there aren't any new results
</label>
</div>
<div class="action-panel-control-wrap option-text-in-email-wrap">
<label for="saved-search-email-text" class="action-panel-label">
Optional text in email:
</label>
<textarea name="saved-search-email-text"
id="saved-search-email-text"
class="saved-search-email-text"></textarea>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Saving..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Save
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your saved search' panel"
ref="linksrc=close_saved_search_panel"
aria-controls="saved-search-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Create a file for external citation management software
</h2>
<form id="citation-manager-action-panel-form"
class="action-panel-content action-form"
action="/results-export-ids/"
data-by-search-action="/results-export-search-data/"
data-by-ids-action="/results-export-ids/"
method="post"
data-by-search-method="post"
data-by-ids-method="post">
<input type="hidden" name="csrfmiddlewaretoken" value="F4UVkTya1sspKg7jkjMUcrhertQ1YorRWRE0XJ1wB3fTEHd9XCpWGzNSZxydRZZb">
<input name="results-format" type="hidden" value="pubmed"/>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="save">
Create file
</button>
<button class="action-panel-cancel"
aria-label="Close 'Send citations to citation manager' panel"
ref="linksrc=close_citation_manager_panel"
aria-controls="citation-manager-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your RSS Feed
</h2>
<form id="rss-action-panel-form"
class="rss-action-panel-form action-panel-content action-form"
data-create-rss-feed-url="/create-rss-feed-url/"
data-search-form-term-value="">
<input type="hidden" name="csrfmiddlewaretoken" value="F4UVkTya1sspKg7jkjMUcrhertQ1YorRWRE0XJ1wB3fTEHd9XCpWGzNSZxydRZZb">
<div class="action-panel-control-wrap">
<label for="rss-name" class="action-panel-label required-field-asterisk">
Name of RSS Feed:
</label>
<input maxlength="200"
placeholder="Name"
type="text"
name="rss-name"
id="rss-name"
class="rss-name"
value=''
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="rss-limit-wrap">
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="rss-limit" class="action-panel-label">
Number of items displayed:
</label>
<select id="rss-limit" class="no-border-panel-selector rss-limit">
<option value="5">5</option>
<option value="10">10</option>
<option value="15" selected="selected">15</option>
<option value="20">20</option>
<option value="50">50</option>
<option value="100">100</option>
</select>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Creating..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Create RSS
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your RSS' panel"
ref="linksrc=close_rss_panel"
aria-controls="rss-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
<div class="action-panel-control-wrap rss-link-copy-wrap">
<label for="rss-link" class="usa-sr-only">RSS Link</label>
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
<button
type="button"
disabled
class="rss-link-copy-button disabled"
data-ga-category="save_share"
data-ga-action="rss"
data-ga-label="copy">
Copy
</button>
</div>
</form>
</div>
</div>
</div>
</div>
<div class="article-page" id="article-page" data-article-pmid="18521183">
<aside class="page-sidebar">
<div class="inner-wrap">
<div class="full-text-links">
<div class="full-view">
<h3 class="title">
Full text links
</h3>
<div class="full-text-links-list">
<a class="link-item
dialog-focus"
href="https://doi.org/10.1172/JCI34088"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=6619&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=18521183&amp;db=pubmed&amp;nlmid=7802877"
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American Society for Clinical Investigation
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/18521183/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=18521183&amp;db=pubmed&amp;nlmid=7802877"
title="Free full text at PubMed Central"
data-ga-category="full_text"
data-ga-action="PMC"
data-ga-label="18521183"
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Free PMC article
</span></a>
</div>
</div>
<div class="short-view">
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
Full text links
</a>
</div>
</div>
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
aria-label="Open dialog with citation text in different styles"
data-ga-category="save_share"
data-ga-action="cite"
data-ga-label="open"
data-all-citations-url="/18521183/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/18521183/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="18521183" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
aria-label="Save article in MyNCBI collections."
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_button"
data-collections-open-dialog-enabled="false"
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F18521183%2F%23open-collections-dialog"
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
class="dialog collections-dialog"
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-myncbi-max-collection-name-length="100"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="F4UVkTya1sspKg7jkjMUcrhertQ1YorRWRE0XJ1wB3fTEHd9XCpWGzNSZxydRZZb"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
id="collections-action-dialog-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
id="collections-action-dialog-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
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<p>
Hereditary sensory and autonomic neuropathy type II (HSANII) is an early-onset autosomal recessive disorder characterized by loss of perception to pain, touch, and heat due to a loss of peripheral sensory nerves. Mutations in hereditary sensory neuropathy type II (HSN2), a single-exon ORF originally identified in affected families in Quebec and Newfoundland, Canada, were found to cause HSANII. We report here that HSN2 is a nervous system-specific exon of the with-no-lysine(K)-1 (WNK1) gene. WNK1 mutations have previously been reported to cause pseudohypoaldosteronism type II but have not been studied in the nervous system. Given the high degree of conservation of WNK1 between mice and humans, we characterized the structure and expression patterns of this isoform in mice. Immunodetections indicated that this Wnk1/Hsn2 isoform was expressed in sensory components of the peripheral nervous system and CNS associated with relaying sensory and nociceptive signals, including satellite cells, Schwann cells, and sensory neurons. We also demonstrate that the novel protein product of Wnk1/Hsn2 was more abundant in sensory neurons than motor neurons. The characteristics of WNK1/HSN2 point to a possible role for this gene in the peripheral sensory perception deficits characterizing HSANII.
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<img class="figure-thumb" itemprop="thumbnail"
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src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5d4/2439463/baa41525d388/JCI0834088.f1.gif"
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<p> Figure 1. Mutations in the <i> WNK1/HSN2 </i> gene. </p>
</strong>
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<strong class="figure-label">
<p> Figure 1. Mutations in the <i> WNK1/HSN2 </i> gene. </p>
</strong>
<div class="figure-caption-contents"><p> ( <b> A </b> ) Segregation of the 2 mutations… </p></div>
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<figcaption id="figure-caption-0" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 1. Mutations in the <i>WNK1/HSN2</i> gene.
</strong>
<div class="figure-caption-contents">(<b>A</b>) Segregation of the 2 mutations identified in the nuclear family. The single affected individual has compound heterozygous mutations. Sequencing traces show the 1-bp deletion (639delA, Arg214fsX215) identified in <i>HSN2</i> (<b>B</b>) and the 2-bp deletion (1584_1585delAG, Asp531fsX547) identified in exon 6 of <i>WNK1</i> (<b>C</b>), with sequencing traces from a normal control. mut, mutated sequencing trace; wt, control sequencing trace.</div>
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<img class="figure-thumb" itemprop="thumbnail"
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<p> Figure 2. RNA expression analyses of <i> Hsn2… </i> </p>
</strong>
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<strong class="figure-label">
<p> Figure 2. RNA expression analyses of <i> Hsn2 </i> messenger. </p>
</strong>
<div class="figure-caption-contents"><p> ( <b> A </b> ) Northern blotting of <i> Hsn2… </i> </p></div>
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<figcaption id="figure-caption-1" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 2. RNA expression analyses of <i>Hsn2</i> messenger.
</strong>
<div class="figure-caption-contents">(<b>A</b>) Northern blotting of <i>Hsn2</i> mouse tissues. The membrane was hybridized with <i>Hsn2</i> probe (top) before it was stripped and rehybridized with a β-actin probe (bottom). (<b>B</b>) RT-PCR amplifications between putative exon 8B (primer 2) and <i>Hsn2</i> (primer 3b). (<b>C</b>) Diagram of <i>Wnk1</i> encompassing <i>Hsn2</i>. Below are the numbered primers (Supplemental Table 1). The positions of <i>Wnk1</i> promoters are indicated by black arrows, and the sites detected by anti-HSN2 and anti-WNK1 (Alpha Diagnostic International) are indicated in red. Kin. D., WNK1 kinase domain. (<b>D</b>) RT-PCR amplifications from brain, spinal cord, DRG, sciatic nerve, kidney, testis, lung, and spleen cDNA. Bottom: Amplifications between exon 8 (primer 1) and <i>Hsn2</i> (primer 3a). Top: Amplifications between <i>Hsn2</i> (primer 4) and exon 10 (primer 5). Arrows 1, 2, and 3 are, respectively, at 250, 420, and 160 bp. (<b>E</b>) RT-PCR amplifications between <i>Hsn2</i> and upstream and downstream region of <i>Wnk1</i>. Left: RT-PCR between a region upstream to the 5′UTR of P1 (primer 5′UTRP1) and <i>Hsn2</i> (primer 3a) in DRG. The same panel shows the amplification between the same 5′UTR of the P1 region and exon 6 in the kidney. Middle: Amplifications between <i>Hsn2</i> (primer 4) and exon 16 (primer 11). Arrows 1, 2, 3, and 4 are, respectively, at approximately 2.2 kb, 950 bp, 650 bp, and approximately 3.8 kb. Right: Amplifications between <i>Hsn2</i> (primer 4) and exon 24 (primer not shown in <b>B</b>). (<b>F</b>) Comparison of <i>Wnk1/Hsn2</i> isoforms with the most common isoform of <i>Wnk1</i>.</div>
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src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5d4/2439463/15c015dd6876/JCI0834088.f3.gif"
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<strong class="figure-label">
<p> Figure 3. Flanking junction sites of the… </p>
</strong>
</div>
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<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 3. Flanking junction sites of the novel alternatively spliced <i> WNK1/HSN2 </i> isoforms. </p>
</strong>
<div class="figure-caption-contents"><p> ( <b> A </b> )… </p></div>
</div>
<figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 3. Flanking junction sites of the novel alternatively spliced <i>WNK1/HSN2</i> isoforms.
</strong>
<div class="figure-caption-contents">(<b>A</b>) RACE revealed that exon 8B was specifically spliced in some transcripts from mouse brain and spinal cord and the amino acids encoded by this mouse putative exon 8B of the longer <i>Wnk1/Hsn2</i> isoform are highly conserved across species. A comparison of the amino acids encoded by the exon 8B ORF in the mouse was made with different species/taxa (chicken, <i>Xenopus</i>, and zebrafish), and greater than 95% residues are fully or highly conserved (an asterisk below the residues indicates those that are fully conserved across the different taxa/species). (<b>B</b>) The amino acid sequences of the splice acceptor and splice donor sites that flank the <i>HSN2</i> exon are highly conserved across species. The regions in blue represent the sequence flanking <i>HSN2</i>, whereas the regions indicated in black are spliced out during mRNA maturation. Splice acceptor and donor sites are in bold characters. The sequences presented were obtained from the UCSC Genome Bioinformatics Browser (<ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://genome.ucsc.edu">
http://genome.ucsc.edu</ext-link>).</div>
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id="article-image-3"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5d4/2439463/ab6be70a5339/JCI0834088.f4.gif"
alt="Figure 4" />
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<strong class="figure-label">
<p> Figure 4. Separate Western immunodetections of WNK1… </p>
</strong>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 4. Separate Western immunodetections of WNK1 and WNK1/HSN2. </p>
</strong>
<div class="figure-caption-contents"><p> Various mouse tissues from adult or… </p></div>
</div>
<figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 4. Separate Western immunodetections of WNK1 and WNK1/HSN2.
</strong>
<div class="figure-caption-contents">Various mouse tissues from adult or E13 animals were loaded and detected with anti-WNK1 (Alpha Diagnostic International) (top) or with IgG purified anti-HSN2 antibody (middle). Expression of WNK1 was observed in all the lysates, and the expression of WNK1/HSN2 was limited to lysates from neuronal tissues. The membrane detected in the top panel was stripped and then detected with the second antibody. An anti-actin antibody was used to confirm that the loading protein was equal in different lanes (bottom).</div>
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<img class="figure-thumb" itemprop="thumbnail"
id="article-image-4"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5d4/2439463/15209f9d724f/JCI0834088.f5.gif"
alt="Figure 5" />
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<strong class="figure-label">
<p> Figure 5. WNK1/HSN2 histological immunodetections. </p>
</strong>
<div class="figure-caption-contents"><p> ( <b> A… </b> </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 5. WNK1/HSN2 histological immunodetections. </p>
</strong>
<div class="figure-caption-contents"><p> ( <b> A </b> ) Immunohistochemistry detection of adult mouse DRG (from… </p></div>
</div>
<figcaption id="figure-caption-4" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 5. WNK1/HSN2 histological immunodetections.
</strong>
<div class="figure-caption-contents">(<b>A</b>) Immunohistochemistry detection of adult mouse DRG (from L5 sections) with anti-HSN2 antiserum (red). A clear immunoreactive signal is visible in the satellite cells (arrows) and in some of the neuronal somata (arrowheads). (<b>B</b>) Overlaid images of the detections with anti-HSN2 (red in <b>A</b>), a mix of axonal markers (SMI-31/32 mix; green), and nuclear staining (TOTO-3 iodide; blue). Colocalization of the signals (yellow overlay) shows that WNK1/HSN2 is expressed in some of the axonal fiber and satellite cells, which surround the neuronal somata (arrows). (<b>C</b>) Adult mouse sciatic nerve cross sections detected with the anti-HSN2 antiserum (red) show the presence of the protein in a mosaic distribution of axons. (<b>D</b>) Overlaid images of the detection with anti-HSN2 (red in <b>C</b>), the axonal markers (green), and nuclear staining (blue) show that not all axonal fibers express WNK1/HSN2 (yellow) and that some do not express WNK1/HSN2 (green). Cross sections of dorsal roots through which sensory axons pass (<b>E</b>) and of ventral roots through which motor axons transit (<b>F</b>) were detected with anti-HSN2 (red) and the axonal marker (green in <b>E</b> and <b>F</b>, insets). The majority of motor neuron axonal fibers showed weak or no WNK1/HSN2 signal. In contrast, the HSN2 signal was strong in most of the axonal fibers of the sensory neurons in the dorsal roots. Original magnification of insets, ×400.</div>
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<p> Figure 6. WNK1/HSN2 protein expression in the… </p>
</strong>
</div>
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<strong class="figure-label">
<p> Figure 6. WNK1/HSN2 protein expression in the adult mouse CNS. </p>
</strong>
<div class="figure-caption-contents"><p> ( <b> A </b> ) Low-magnification image… </p></div>
</div>
<figcaption id="figure-caption-5" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 6. WNK1/HSN2 protein expression in the adult mouse CNS.
</strong>
<div class="figure-caption-contents">(<b>A</b>) Low-magnification image of immunohistochemistry detections of adult mouse spinal cord cross section with anti-HSN2 antiserum. The anti-HSN2 antiserum gave a strong signal (red) in the superficial layers (LI and LII) of the dorsal horn, the dorsolateral funiculus (DLF), the lateral funiculus (LF), and the Lissauer tract (LT). (<b>B</b>) Overlaid images of the HSN2 signal (red in <b>A</b>), the signal from the anti–SMI-31/32 axonal marker (green), and the nuclear fluorescent labeling (blue). (<b>C</b>) Immunodetection of LI and LII with anti-HSN2 (red). (<b>D</b>) Overlaid images of the detection of HSN2 (red in <b>C</b>), NeuN (green), and the nuclear labeling (blue). Arrows indicate neurons where the colocalization is observed, confirming the presence of HSN2 protein in cells of this region.</div>
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