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 develop...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1987-07, Vol.237 (4812), p.286-289
Main Authors: Prochazka, Michal, Leiter, Edward H., Serreze, David V., Coleman, Douglas L.
Format: Article
Language:English
Subjects:
Alleles
Animals
Biochemistry
Chromosome Mapping
Chromosomes
Diabetes
Diabetes complications
Diabetes mellitus
Diabetes Mellitus, Type 1 - genetics
Diabetes Mellitus, Type 1 - immunology
Diseases
Genes, Recessive
Genetic aspects
Genetic disorders
Genetic loci
Genetics
Insulin
Islets of Langerhans - immunology
Medical research
Mice
Mice, Inbred Strains
Mice, Mutant Strains
Polygenic inheritance
Polymorphism, Genetic
Polymorphism, Restriction Fragment Length
Recessive genes
T lymphocytes
T-Lymphocytes - physiology
Type 1 diabetes mellitus
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Summary: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-1$^{\text{s}}$, is tightly linked to the H-2K locus on chromosome 17; another, Idd-2$^{\text{s}}$, is localized proximal to the Thy-1/Alp-1 cluster on chromosome 9. Segregation of a third, Idd-3$^{\text{s}}$, could be shown in a second backcross. Neither Idd-1$^{\text{s}}$ nor Idd-2$^{\text{s}}$ 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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.2885918