Three recessive loci required for insulin-dependent diabetes in nonobese diabetic mice.
A polygenic basis for susceptibility to insulin-dependent diabetes in nonobese diabetic (NOD) mice has been established by outcross to a related inbred strain, nonobese normal (NON). Analysis of first and second backcross progeny has shown that at least three recessive genes are required for development of overt diabetes. One, Idd-1s, is tightly linked to the H-2K locus on chromosome 17; another, Idd-2s, is localized proximal to the Thy-1/Alp-1 cluster on chromosome 9. Segregation of a third, Idd-3s, could be shown in a second backcross. Neither Idd-1s nor Idd-2s could individually be identified as the locus controlling insulitis; leukocytic infiltrates in pancreas were common in most asymptomatic BC1 mice. Both F1 and BC1 mice exhibited the unusually high percentage of splenic T lymphocytes characteristic of NOD, suggesting dominant inheritance of this trait. The polygenic control of diabetogenesis in NOD mice, in which a recessive gene linked to the major histocompatibility complex is but one of several controlling loci, suggests that similar polygenic interactions underlie this type of diabetes in humans.
D000818:Animals; D002874:Chromosome Mapping; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D005808:Genes, Recessive; D007515:Islets of Langerhans / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D013601:T-Lymphocytes / Q000502:physiology