Submitted to: Midwestern Section of the American Society of Animal Science
Publication Type: Abstract Only
Publication Acceptance Date: 11/26/2004
Publication Date: 9/1/2005
Citation: Ferrell, A.D., Allan, M.F., Pomp, D. 2005. Genetics of gene expression of the insulin signaling pathway in polygenic obesity [abstract]. Journal of Animal Science. 83(Supplement 2):44.
Technical Abstract: Adequate characterization of complex traits such as growth and body composition will require innovative methods for determining genetic and physiological control mechanisms. Our objective is to utilize a mouse model, displaying polygenic obesity, to elucidate regulatory roles of specific loci in the insulin signaling pathway. Transcriptome mapping, a method to combine microarray analysis with QTL mapping, was used to evaluate gene expression endo-phenotypes within a QTL mapping population of M16/ICR F2 mice. The M16 line of mice is a result of selection for rapid growth rate from 3 to 6 weeks of age. These mice exhibit hyperphagia, hyperglycemia, NIDDM and are moderately obese compared to the ICR control line. mRNA was extracted from liver tissue of 8-week old F2 male mice with extreme body fat phenotypes (n=88, selected from 1200), and hybridized to probes for 96 well-characterized genes in the insulin signaling pathway (GEArray by SuperArray®). Probes on this macroarray represented insulin receptor-associated proteins, PI-3 kinase and MAPK pathways, and targets for insulin signaling, PPARg and SREBP-1. Gene expression endo-phenotypes were analyzed in QTL Express with multiple normalization methods. Evaluation of map positions of the resulting expression QTL (eQTL) relative to map positions for loci represented on the macroarray revealed potential cis- or trans-acting eQTL. Preliminary results indicate potential cis-acting eQTL for Ptprf on chromosome 4, Ptpn11 on chromosome 5 and Slc2a4 on chromosome 11. A potential eQTL representing a putative master regulator of several genes in the insulin signaling pathway exists on chromosome 4. Differences in gene expression and potential eQTL will be validated with Real-Time PCR (taqman). Characterization of endo-phenotypes in relation to the physiological function of the insulin signaling pathway in liver tissue may contribute to a better understanding of the overall regulation of growth and body composition.