Analysis of genetic basis for islet-specific autoimmunity and the applecation to prevention and treatment of type 1 diabetes

1型糖尿病是一种针对胰岛中产生胰岛素的β细胞的组织特异性自身免疫性疾病。为了阐明β细胞特异性破坏的机制和1型糖尿病治疗的应用，我们通过1型糖尿病候选基因与多种器官特异性自身免疫性疾病（1型糖尿病、Graves病、桥本甲状腺炎和斑秃）的关联研究，确定了胰岛特异性自身免疫性反应的遗传因素，包括Mafa基因。然后，我们通过速度基因法建立了Mafa基因敲除NOD小鼠。与杂合子和野生型相比，Mafa基因敲除NOD小鼠1型糖尿病的累积发病率在敲除等位基因的纯合子中得到显著保护，提示Mafa基因在体内对1型糖尿病的发展起着关键作用。

Type 1 diabetes is a tissue-specific autoimmune disease against insulin-producing beta cells in pancreatic islets. To clarify the mechanisms of beta cell-specific destruction and the application of treatment for type 1 diabetes, we identified genetic factors, including Mafa gene, for islet-specific autoimmune response by association studies of candidate genes for type 1 diabetes with multiple organ-specific autoimmune diseases (type 1 diabetes, Graves' disease, Hashimoto thyroiditis and alopecia areata). Then, we established the Mafa knockout NOD mouse by speed congenic protocol. The cumulative incidence of type 1 diabetes in Mafa knockout NOD mouse was significantly protected in homozygotes of knockout allele in comparison with heterozygotes and wild type, suggesting the critical role of Mafa gene on the development of type 1 diabetes in vivo.