Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Nat Commun ; 6: 6748, 2015 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-25849081

RESUMO

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 ß-cells are unresponsive even to high dose of Type I interferon. Reversal of virus-induced diabetes could be achieved by ß-cell-specific Tyk2 gene expression. Thus, reduced Tyk2 gene expression in pancreatic ß-cells due to natural mutation is responsible for susceptibility to virus-induced diabetes.


Assuntos
Infecções por Cardiovirus/genética , Diabetes Mellitus Experimental/genética , Vírus da Encefalomiocardite , Células Secretoras de Insulina/metabolismo , RNA Mensageiro/metabolismo , TYK2 Quinase/genética , Animais , Diabetes Mellitus Experimental/virologia , Expressão Gênica , Predisposição Genética para Doença , Interferon Tipo I , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Camundongos Knockout , Mutação , TYK2 Quinase/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...