International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


Mr Mark F Allan
University of Nebraska
Dept of Animal Sciences
Animal Sciences Building
UNL, East Campus
Lincoln 68583-09018 USA

Co-Authors:  1)Sarath G, 2)Eisen EJ, 3)Pomp D
Institutions:   1)University of Nebraska, Department of Biochemistry, 2)North Carolina State University, Department of Animal Science, 3)University of Nebraska, Department of Animal Science

Proteomic dissection of energy balance in polygenic mice selected for rapid post-weaning gain

Positional cloning of genes underlying QTL (Quantitative Trait Loci) for complex traits has had little success. Our objective is to integrate proteomic analysis with genomic methods, to facilitate discovery of both predisposition and physiologically regulating genes related to energy balance in a polygenic model of obesity. We used an outbred line (M16) selected for 3-6 wk gain for 27 generations, from a base population of ICR mice. M16 mice have larger body weights, exhibit hyperphagia accompanied by moderate obesity, and are hyperglycemic/hyperinsulinemic relative to ICR mice. Protein levels in hepatic lysate pools representing six (8-wk old) males from each line (M16, ICR) were analyzed with 792 different monoclonal antibodies in triplicate (BD Transduction Laboratories, USA). Results indicate putative differences in levels of many proteins in the receptor tyrosine kinase signaling pathway (e.g. PTEN, CK II beta, AF6) and in several proteins mediating apoptosis (e.g. GOK/Stim1, hILP/XIAP, DAP3), along with other additional promising candidates (e.g. E2F1, ET-1r, elF-6). High throughput protein quantification assays will be developed to phenotype a large (n=1100) M16 x ICR F2 population. Such analysis will facilitate correlation of predisposition (QTL) genes with those regulating key physiological events controlling energy balance, and will enable a better understanding of the overall genetic architecture of complex traits.

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