The iddm4 locus segregates with diabetes susceptibility in congenic WF.iddm4 rats
Department of Medicine, Diabetes Division; Department of Pathology
Adoptive Transfer; Alleles; Animals; *Chromosome Mapping; Diabetes Mellitus, Type 1; Disease Models, Animal; Genetic Markers; Genetic Predisposition to Disease; Homozygote; Islets of Langerhans; Pancreatic Diseases; Rats; Rats, Mutant Strains
Life Sciences | Medicine and Health Sciences
Viral antibody-free BBDR and WF rats never develop spontaneous diabetes. BBDR rats, however, develop autoimmune diabetes after perturbation of the immune system, e.g., by viral infection. We previously identified a disease-susceptibility locus in the BBDR rat, iddm4, which is associated with the development of autoimmune diabetes after treatment with polyinosinic:polycytidylic acid and an antibody that depletes ART2(+) regulatory cells. We have now developed lines of congenic WF.iddm4 rats and report that in an intercross of N5 generation WF.iddm4 rats, approximately 70% of animals either homozygous or heterozygous for the BBDR origin allele of iddm4 became hyperglycemic after treatment to induce diabetes. Fewer than 20% of rats expressing the WF origin allele of iddm4 became diabetic. Testing the progeny of various recombinant N5 WF.iddm4 congenic rats for susceptibility to diabetes suggests that iddm4 is centered on a small segment of chromosome 4 bounded by the proximal marker D4Rat135 and the distal marker D4Got51, an interval of <2.8 cM. The allele at iddm4 has 79% sensitivity and 80% specificity in prediction of diabetes in rats that are segregating for this locus. These characteristics suggest that iddm4 is one of the most powerful non-major histocompatibility complex determinants of susceptibility to autoimmune diabetes described to date.
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Citation: Diabetes. 2002 Nov;51(11):3254-62.
Mordes, John P.; Leif, Jean H.; Novak, Stephen; DeScipio, Cheryl; Greiner, Dale L.; and Blankenhorn, Elizabeth P., "The iddm4 locus segregates with diabetes susceptibility in congenic WF.iddm4 rats" (2002). Open Access Articles. 483.