References
Query Results -- Details
MGI Accession ID: MGI:2447908
J Number: J:80976
Other Accession IDs:
Title: Lipoatrophic diabetes in Irs1(-/-)/Irs3(-/-) double knockout mice.
Authors: Laustsen PG; Michael MD; Crute BE; Cohen SE; Ueki K; Kulkarni RN; Keller SR; Lienhard GE; Kahn CR
Journal: Genes Dev
Volume: 16
Issue: 24
Date: 2002 Dec 15
Year: 2002
Pages: 3213-22
Review Status: Peer Reviewed
Abstract:
Based on the phenotypes of knockout mice and cell lines, as well as pathway-specific analysis, the insulin receptor substrates IRS-1, IRS-2, IRS-3, and IRS-4 have been shown to play unique roles in insulin signal transduction. To investigate possible functional complementarity within the IRS family, we generated mice with double knockout of the genes for IRS-1/IRS-3 and IRS-1/IRS-4. Mice with a combined deficiency of IRS-1 and IRS-4 showed no differences from Irs1(-/-) mice with respect to growth and glucose homeostasis. In contrast, mice with a combined deficiency of IRS-1 and IRS-3 developed early-onset severe lipoatrophy associated with marked hyperglycemia, hyperinsulinemia, and insulin resistance. However, in contrast to other models of lipoatrophic diabetes, there was no accumulation of fat in liver or muscle. Furthermore, plasma leptin levels were markedly decreased, and adenovirus-mediated expression of leptin in liver reversed the hyperglycemia and hyperinsulinemia. The results indicate that IRS-1 and IRS-3 play important complementary roles in adipogenesis and establish the Irs1(-/-)/Irs3(-/-) double knockout mouse as a novel model of lipoatrophic diabetes.
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