References
Query Results -- Details
MGI Accession ID: MGI:85885
J Number: J:38502
Other Accession IDs:
Title: Development of a novel polygenic model of NIDDM in mice heterozygous for IR and IRS-1 null alleles.
Authors: Bruning JC; Winnay J; Bonner-Weir S; Taylor SI; Accili D; Kahn CR
Journal: Cell
Volume: 88
Issue: 4
Date: 1997 Feb 21
Year: 1997
Pages: 561-72
Review Status: Peer Reviewed
Abstract:
NIDDM is a polygenic disease characterized by insulin resistance in muscle, fat, and liver, followed by a failure of pancreatic beta cells to adequately compensate for this resistance despite increased insulin secretion. Mice double heterozygous for null alleles in the insulin receptor and insulin receptor substrate-1 genes exhibit the expected approximately 50% reduction in expression of these two proteins, but a synergism at a level of insulin resistance with 5- to 50-fold elevated plasma insulin levels and comparable levels of beta cell hyperplasia. At 4-6 months of age, 40% of these double heterozygotes become overtly diabetic. This NIDDM mouse model in which diabetes arises in an age-dependent manner from the interaction between two genetically determined, subclinical defects in the insulin signaling cascade demonstrates the role of epistatic interactions in the pathogenesis of common diseases with non-Mendelian genetics.
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