Alternative titles; symbols
HGNC Approved Gene Symbol: NKX2-2
Cytogenetic location: 20p11.22 Genomic coordinates (GRCh38) : 20:21,511,017-21,522,689 (from NCBI)
The morphogenesis of the central nervous system is thought to be established by an integrated network of regulatory factors. Vertebrate homologs of Drosophila segmentation and homeotic (Hox) genes are among the numerous regulatory genes expressed at high levels in the central nervous system. Homeobox-containing genes are a large family of transcription factors that are distinguished by a 60-amino acid evolutionarily conserved DNA-binding homeodomain. See 142950 for additional background information on homeobox genes.
By screening a cosmid DNA library at low stringency with a probe from the homeobox-containing TTF1 (600635), Price et al. (1992) obtained a partial mouse cDNA for Nkx2.2. By RNAase mapping experiments, they found that Nkx2.2 transcripts are in localized domains of the brain during mouse embryogenesis. Hartigan and Rubenstein (1996) isolated a complete cDNA clone for Nkx2.2 which encodes a 273-amino acid protein. By immunofluorescence experiments, Sussel et al. (1998) determined that, within the pancreas, Nkx2.2 is expressed in insulin-producing beta cells, glucagon-producing alpha cells, and pancreatic polypeptide (PP)-secreting cells of the islet, but not in somatostatin-producing delta cells.
By screening pools of PAC DNA with PCR primers for mouse Nkx2.2, Furuta et al. (1998) isolated a human NKX2B cDNA, which encodes a protein that shows 98% sequence identity to mouse Nkx2.2.
Holland et al. (2007) stated that the NKX2-2 and NKX2-8 (603245) genes are collectively orthologous to Drosophila vnd and comprise the Nk2.2 gene family.
Furuta et al. (1998) determined that the NKX2B gene contains 2 exons that span approximately 2.5 kb.
By FISH, Furuta et al. (1998) mapped the NKX2B gene to chromosome 20p11.
Wang et al. (2000) stated that linkage of the Nkx2.1 and Nkx2.9 genes on mouse chromosome 12 and of the Nkx2.4 (NKX2D; 607808) and Nkx2.2 genes on mouse chromosome 2 suggests that these gene pairs represent paralogous clusters, as initially defined for duplicated Hox gene clusters in vertebrates. Each Nkx2 protein is more related to its duplicated partner on another chromosome than to its linked partner. This supports a model in which an ancient gene was duplicated to form a tandem gene pair, which was then duplicated to another chromosomal locus at a later time, forming a paralogous pair.
Ding et al. (2003) presented evidence suggesting that Nkx2.2 acts downstream of Shh (600725) and upstream of Lmx1b (602575) in a signaling cascade to direct the development, specification, and/or differentiation of 5-HT (5-hydroxytryptamine) neurons in the central nervous system in mice.
Furuta et al. (1998) found no association between NKX2B mutations and maturity-onset diabetes of the young in 57 unrelated Japanese subjects.
Mice homozygous for a targeted disruption in the Nkx2.2 gene die within a few days of birth with severe hyperglycemia (Sussel et al., 1998).
Ding, Y.-Q., Marklund, U., Yuan, W., Yin, J., Wegman, L., Ericson, J., Deneris, E., Johnson, R. L., Chen, Z.-F. Lmx1b is essential for the development of serotonergic neurons. Nature Neurosci. 6: 933-938, 2003. [PubMed: 12897786] [Full Text: https://doi.org/10.1038/nn1104]
Furuta, H., Horikawa, Y., Iwasaki, N., Hara, M., Sussel, L., Le Beau, M. M., Davis, E. M., Ogata, M., Iwamoto, Y., German, M. S., Bell, G. I. Beta-cell transcription factors and diabetes: mutations in the coding region of the BETA2/NeuroD1 (NEUROD1) and Nkx2.2 (NKX2B) genes are not associated with maturity-onset diabetes of the young in Japanese. Diabetes 47: 1356-1358, 1998. [PubMed: 9703340] [Full Text: https://doi.org/10.2337/diab.47.8.1356]
Hartigan, D. J., Rubenstein, J. L. The cDNA sequence of murine Nkx-2.2. Gene 168: 271-272, 1996. [PubMed: 8654958] [Full Text: https://doi.org/10.1016/0378-1119(95)00745-8]
Holland, P. W. H., Booth, H. A. F., Bruford, E. A. Classification and nomenclature of all human homeobox genes. BMC Biol. 5: 47, 2007. Note: Electronic Article. [PubMed: 17963489] [Full Text: https://doi.org/10.1186/1741-7007-5-47]
Price, M., Lazzaro, D., Pohl, T., Mattei, M. G., Ruther, U., Olivo, J. C., Duboule, D., Di Lauro, R. Regional expression of the homeobox gene Nkx-2.2 in the developing mammalian forebrain. Neuron 8: 241-255, 1992. [PubMed: 1346742] [Full Text: https://doi.org/10.1016/0896-6273(92)90291-k]
Sussel, L., Kalamaras, J., Hartigan-O'Connor, D. J., Meneses, J. J., Pedersen, R. A., Rubenstein, J. L., German, M. S. Mice lacking the homeodomain transcription factor Nkx2.2 have diabetes due to arrested differentiation of pancreatic beta cells. Development 125: 2213-2221, 1998. [PubMed: 9584121] [Full Text: https://doi.org/10.1242/dev.125.12.2213]
Wang, C.-C., Brodnicki, T., Copeland, N. G., Jenkins, N. A., Harvey, R. P. Conserved linkage of NK-2 homeobox gene pairs Nkx2-2/2-4 and Nkx2-1/2-9 in mammals. Mammalian Genome 11: 466-468, 2000. [PubMed: 10818213] [Full Text: https://doi.org/10.1007/s003350010089]