Faculty Research 1980 - 1989

Title

Three recessive loci required for insulin-dependent diabetes in nonobese diabetic mice.

Document Type

Article

Publication Date

1987

Keywords

Chromosome-Mapping, Diabetes-Mellitus-Insulin-Dependent Genes-Recessive, Islands-of-Langerhans, Mice, Mice-Inbred-Strains, Mice-Mutant-Strains, Polymorphism-(Genetics), Restriction-Fragment-Length-Polymorphisms

JAX Source

Science. 1987 Jul 17; 237(4812):286-9.

Grant

AM36175, AM27722, AM14461

Abstract

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.