International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


POSTER 75 - GENETICS OF GENE EXPRESSION OF THE INSULIN SIGNALING PATHWAY IN POLYGENIC OBESITY

Ferrell AD, Allan MF, Pomp D

University of Nebraska, Lincoln, United States

An estimated 65% of U.S. adults are overweight and ~30% are obese.  Polygenic mouse models play a pivotal role in understanding the roles of specific loci in genetic predisposition to obesity.  We are applying transcriptome mapping, whereby gene expression phenotypes are evaluated within a QTL mapping population, to identify candidate genes for obesity predisposition and to better understand the genetic architecture of complex traits in general.  Using a cross between the M16 (selected for rapid growth rate for 27 generations) and ICR (unselected control) lines, we have created a large (n=1200) F2 population segregating for phenotypes relevant to obesity, food consumption, and NIDDM. We are hybridizing mRNA, extracted from liver samples of F2 mice (n=88) with extreme body fat phenotypes, to probes for 96 well-characterized genes in the insulin signaling pathway.  This macroarray (GEArray Q Series, SuperArray) contains genes representing insulin receptor-associated proteins, the PI-3 kinase and MAPK pathways, primary targets for insulin signaling, secondary effector targets for insulin signaling, and targets for PPARg and SREBP-1. Analyses for gene expression endo-phenotypes and primary energy-balance phenotypes will be merged, and evaluated relative to the overall genetic correlation structure of the population, to reveal cis- and trans-acting expression QTL that combine to regulate the insulin signaling pathway and contribute to the overall regulation of polygenic obesity.

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