title: Normal incidence of diabetes in NOD mice tolerant to glutamic acid decarboxylase.
abstract: Experiments in nonobese diabetic (NOD) mice that lacked expression of glutamic acid decarboxylase (GAD) in beta 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.
authors.affiliation: Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Elmar
authors.initials: E
authors.lastname: Jaeckel
authors.forename: Ludger
authors.initials: L
authors.lastname: Klein
authors.forename: Natalia
authors.initials: N
authors.lastname: Martin-Orozco
authors.forename: Harald
authors.initials: H
authors.lastname: von Boehmer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens; D001483:Base Sequence; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology* / Q000276:immunology*; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D005260:Female; D005968:Glutamate Decarboxylase / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance; D007328:Insulin / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D001324:Autoantigens; D000939:Epitopes; D007328:Insulin; D011993:Recombinant Fusion Proteins; D005968:Glutamate Decarboxylase