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Science 14 May 1999:
Vol. 284. no. 5417, pp. 1183 - 1187
DOI: 10.1126/science.284.5417.1183
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Reports

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

Ji-Won Yoon, 123* Chang-Soon Yoon, 1 Hye-Won Lim, 1 Qi Quan Huang, 1 Yup Kang, 2 Kwang Ho Pyun, 4 Kensuke Hirasawa, 1 Robert S. Sherwin, 3 Hee-Sook Jun 1

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.

1 Laboratory of Viral and Immunopathogenesis of Diabetes, Julia McFarlane Diabetes Research Centre and Department of Microbiology and Infectious Diseases, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
2 Laboratory of Endocrinology, Institute for Medical Science, Department of Endocrinology and Metabolism, School of Medicine, Ajou University, San 5, Wonchon-dong, Paldal-gu, Suwon 442-749, Korea.
3 Diabetes Endocrinology Research Center, School of Medicine, Yale University, 333 Cedar Street, New Haven, CT 06520-8020, USA.
4 Korea Research Institute of Bioscience and Biotechnology, 52 Eueon-dong, Yusong-ku, Taejon 305-333, Korea.
*   To whom correspondence should be addressed. E-mail: yoon{at}ucalgary.ca

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