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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\n                    <jats:italic>Tyrosine kinase 2 (Tyk2)<\/jats:italic>\n                    gene mutations are present in virus-induced diabetes-sensitive SJL and SWR mice. Mice carrying the mutant\n                    <jats:italic>Tyk2<\/jats:italic>\n                    gene on the virus-resistant C57BL\/6 background are highly sensitive to virus-induced diabetes.\n                    <jats:italic>Tyk2<\/jats:italic>\n                    gene expression is strongly reduced in\n                    <jats:italic>Tyk2<\/jats:italic>\n                    -mutant mice, associated with low\n                    <jats:italic>Tyk2<\/jats:italic>\n                    promoter activity, and leads to decreased expression of interferon-inducible genes, resulting in significantly compromised antiviral response.\n                    <jats:italic>Tyk2-<\/jats:italic>\n                    mutant pancreatic \u03b2-cells are unresponsive even to high dose of Type I interferon. Reversal of virus-induced diabetes could be achieved by \u03b2-cell-specific\n                    <jats:italic>Tyk2<\/jats:italic>\n                    gene expression. Thus, reduced\n                    <jats:italic>Tyk2<\/jats:italic>\n                    gene expression in pancreatic \u03b2-cells due to natural mutation is responsible for susceptibility to virus-induced diabetes.\n                  <\/jats:p>","DOI":"10.1038\/ncomms7748","type":"journal-article","created":{"date-parts":[[2015,4,7]],"date-time":"2015-04-07T09:15:06Z","timestamp":1428398106000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Reduced Tyk2 gene expression in \u03b2-cells due to natural mutation determines susceptibility to virus-induced diabetes"],"prefix":"10.1038","volume":"6","author":[{"given":"Kenichi","family":"Izumi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiichiro","family":"Mine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitaka","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miho","family":"Teshima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichiro","family":"Ogawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Kai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshinobu","family":"Kurafuji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanako","family":"Hirakawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiki","family":"Miyakawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruka","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akari","family":"Inada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manami","family":"Hara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisakata","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Akashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyuki","family":"Niho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Ina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasunobu","family":"Yoshikai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keizo","family":"Anzai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teruo","family":"Yamashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Minagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuji","family":"Fujimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironori","family":"Kurisaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Shimoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Katsuta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8790-8358","authenticated-orcid":false,"given":"Seiho","family":"Nagafuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,4,7]]},"reference":[{"key":"BFncomms7748_CR1","doi-asserted-by":"publisher","first-page":"S2","DOI":"10.1038\/485S2a","volume":"485","author":"T Scully","year":"2012","unstructured":"Scully, T. 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