Genetic control of organ-reactive autoantibody production in mice by obesity (ob) diabetes (db) genes.
Inbred strains of mice exhibited genetic and sex-dependent differences in spontaneous production of organ-reactive autoantibodies detected by indirect immunofluorescence. Antitestis autoreactivity was found primarily in sera from C57BL/6J (B6) mice, whereas antigastric autoreactivity was common to both CBA/J and 129/J strains. Autoantibodies against islet cell cytoplasmic antigens (ICAs) were uniquely expressed by C57BL/KsJ (BKs) males. Introduction of the diabetes (db) mutation into these various inbred-strain backgrounds induced expression of ICA, with stronger induction observed in males. The stress imposed by the db or obesity (ob) mutation induced ICA in BKs mice at a higher frequency than in B6 mice; this differential sensitivity was somehow related to a gene linked to the H-2 complex because BKs.B6 H-2b congenic mice resembled B6 mice. The db3J mutation increased the expression of these autoantibodies in 129/J mice, which, like B6, were H-2b and therefore presumably possessed the same H-2-linked inducibility allele as BKs. Cytotoxic autoantibodies against islet cell surface antigens were only observed in C3HeB/FeJ db/db males, and their presence was correlated with beta-cell necrosis. It is concluded that db and/or ob genes appear to play an important role in the production of autoantibodies to islet cells, and sex-linked factor(s) may modify the phenotypic expression of the autoantibodies.
D000818:Animals; D000917:Antibody Formation; D001323:Autoantibodies / Q000032:analysis / Q000235:genetics*; D003920:Diabetes Mellitus / Q000235:genetics* / Q000276:immunology; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000276:immunology; D005260:Female; D005796:Genes; D005838:Genotype; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D009154:Mutation; D009765:Obesity; D009928:Organ Specificity
D001323:Autoantibodies