通过在β细胞中表达或抑制谷氨酸脱羧酶（GAD）来控制非肥胖糖尿病（NOD）小鼠的自身免疫性糖尿病。

Control of autoimmune diabetes in NOD mice by GAD expression or suppression in beta cells.

作者信息

Yoon J W, Yoon C S, Lim H W, Huang Q Q, Kang Y, Pyun K H, Hirasawa K, Sherwin R S, Jun H S

机构信息

Laboratory of Viral and Immunopathogenesis of Diabetes, Julia McFarlane Diabetes Research Centre, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada.

出版信息

Science. 1999 May 14;284(5417):1183-7. doi: 10.1126/science.284.5417.1183.

DOI:10.1126/science.284.5417.1183

PMID:10325232

Abstract

Glutamic acid decarboxylase (GAD) is a pancreatic beta cell autoantigen in humans and nonobese diabetic (NOD) mice. beta Cell-specific suppression of GAD expression in two lines of antisense GAD transgenic NOD mice prevented autoimmune diabetes, whereas persistent GAD expression in the beta cells in the other four lines of antisense GAD transgenic NOD mice resulted in diabetes, similar to that seen in transgene-negative NOD mice. Complete suppression of beta cell GAD expression blocked the generation of diabetogenic T cells and protected islet grafts from autoimmune injury. Thus, beta cell-specific GAD expression is required for the development of autoimmune diabetes in NOD mice, and modulation of GAD might, therefore, have therapeutic value in type 1 diabetes.

摘要

谷氨酸脱羧酶（GAD）是人类和非肥胖糖尿病（NOD）小鼠的胰腺β细胞自身抗原。在两株反义GAD转基因NOD小鼠中，β细胞特异性抑制GAD表达可预防自身免疫性糖尿病，而在另外四株反义GAD转基因NOD小鼠中，β细胞中持续的GAD表达则导致糖尿病，这与转基因阴性的NOD小鼠中所见的情况相似。完全抑制β细胞GAD表达可阻断致糖尿病T细胞的产生，并保护胰岛移植免受自身免疫损伤。因此，β细胞特异性GAD表达是NOD小鼠自身免疫性糖尿病发生所必需的，因此，调节GAD可能对1型糖尿病具有治疗价值。