Diabetes, Vol 37, Issue 9 1287-1293, Copyright © 1988 by American Diabetes Association

ARTICLES

Genetic control of organ-reactive autoantibody production in mice by obesity (ob) diabetes (db) genes

JW Yoon, EH Leiter, DL Coleman, MK Kim, CY Pak, RG McArthur and DA Roncari
Department of Microbiology and Infectious Diseases, University of Calgary, Alberta, Canada.

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.
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