| First Author | Izumi K | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 6748 | PubMed ID | 25849081 |
| Mgi Jnum | J:233414 | Mgi Id | MGI:5784606 |
| Doi | 10.1038/ncomms7748 | Citation | Izumi K, et al. (2015) Reduced Tyk2 gene expression in beta-cells due to natural mutation determines susceptibility to virus-induced diabetes. Nat Commun 6:6748 |
| abstractText | Accumulating evidence suggests that viruses play an important role in the development of diabetes. Although the diabetogenic encephalomyocarditis strain D virus induces diabetes in restricted lines of inbred mice, the susceptibility genes to virus-induced diabetes have not been identified. We report here that novel Tyrosine kinase 2 (Tyk2) gene mutations are present in virus-induced diabetes-sensitive SJL and SWR mice. Mice carrying the mutant Tyk2 gene on the virus-resistant C57BL/6 background are highly sensitive to virus-induced diabetes. Tyk2 gene expression is strongly reduced in Tyk2-mutant mice, associated with low Tyk2 promoter activity, and leads to decreased expression of interferon-inducible genes, resulting in significantly compromised antiviral response. Tyk2-mutant pancreatic beta-cells are unresponsive even to high dose of Type I interferon. Reversal of virus-induced diabetes could be achieved by beta-cell-specific Tyk2 gene expression. Thus, reduced Tyk2 gene expression in pancreatic beta-cells due to natural mutation is responsible for susceptibility to virus-induced diabetes. |
