Control of Autoimmune Diabetes in NOD Mice by GAD Expression or Suppression in β Cells

Abstract

Glutamic acid decarboxylase (GAD) is a pancreatic β cell autoantigen in humans and nonobese diabetic (NOD) mice. β Cell–specific suppression of GAD expression in two lines of antisense GAD transgenic NOD mice prevented autoimmune diabetes, whereas persistent GAD expression in the β 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 β cell GAD expression blocked the generation of diabetogenic T cells and protected islet grafts from autoimmune injury. Thus, β 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.