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Normal Incidence of Diabetes in NOD Mice Tolerant to Glutamic Acid Decarboxylase

Elmar Jaeckel¹, Ludger Klein¹, Natalia Martin-Orozco² and Harald von Boehmer¹

¹ Dana Farber Cancer Institute, Harvard Medical School
² Joslin Diabetes Center, Boston, MA 02115

Address correspondence to Harald von Boehmer, Dana Farber Cancer Institute, Dept. of Cancer Immunology & AIDS, 44 Binney St., Boston, MA 02115. Phone: 617-632-6882; Fax: 617-632-6881; E-mail: harald_von_boehmer{at}dfci.harvard.edu

Experiments in nonobese diabetic (NOD) mice that lacked expression of glutamic acid decarboxylase (GAD) in ß cells have suggested that GAD represents an autoantigen essential for initiating and maintaining the diabetogenic immune response. Several attempts of inducing GAD-specific recessive tolerance to support this hypothesis have failed. Here we report on successful tolerance induction by expressing a modified form of GAD under control of the invariant chain promoter resulting in efficient epitope display. In spite of specific tolerance insulitis and diabetes occurred with normal kinetics indicating that GAD is not an essential autoantigen in the pathogenesis of diabetes.

Key Words: diabetes • NOD mouse • tolerance • GAD65 • autoimmunity

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