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

• Published in: Science (American Association for the Advancement of Science) Vol. 284; no. 5417; pp. 1183 - 1187
• Main Authors: Yoon, Ji-Won, Yoon, Chang-Soon, Lim, Hye-Won, Huang, Qi Quan, Kang, Yup, Pyun, Kwang Ho, Hirasawa, Kensuke, Sherwin, Robert S., Jun, Hee-Sook
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 14.05.1999; American Association for the Advancement of Science
• Subjects: Adoptive Transfer; Animals; Autoantigens - genetics; Autoantigens - immunology; Autoantigens - physiology; Autoimmune diseases; Autoimmunity; Biological and medical sciences; Cell lines; Diabetes; Diabetes complications; Diabetes Mellitus, Type 1 - enzymology; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - pathology; Diabetes. Impaired glucose tolerance; DNA, Antisense; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Gene Expression; Glutamate decarboxylase; Glutamate Decarboxylase - genetics; Glutamate Decarboxylase - immunology; Glutamate Decarboxylase - physiology; Insulin; Insulin - blood; Insulin - metabolism; Islets of Langerhans - enzymology; Islets of Langerhans - immunology; Islets of Langerhans - metabolism; Islets of Langerhans - pathology; Islets of Langerhans Transplantation; Lymphocyte Activation; Male; Medical sciences; Mice; Mice, Inbred NOD; Mice, SCID; Mice, Transgenic; Physiological aspects; Prevention; Splenocytes; T lymphocytes; T-Lymphocytes - immunology; Transgenes; Transgenic animals; Type 1 diabetes; Type 1 diabetes mellitus; Endocrinopathy; Animal model; Enzyme; Pathogenesis; Suppression; Rodentia; Transgenic animal; Autoimmune disease; Lyases; Glutamate decarboxylase; Gene expression; Carbon-carbon lyases; Vertebrata; Regulation(control); Mammalia; Autoantigen; B-Cell; Gene; Mouse; Etiology; Carboxy-lyases; Insulin dependent diabetes; Pancreas
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.284.5417.1183

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.