International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


Gordon RR 1, Pomp D 1, Hunter KW 2

1 University of Nebraska, Lincoln, United States, 2 NCI/NIH, Bethesda, United States

Genetic predisposition to complex traits results from interactive combinations of relatively small effects of genetic variations within a large number of primarily unidentified polygenes, known as quantitative trait loci (QTL).  Given the growing evidence that obesity may increase the risk of susceptibility to certain forms of cancer, we have created a population of F2 mice cosegregating obesity QTL and the MMTV-PyMT transgene, with a primary objective of determining how polygenic obesity influences age at mammary tumor onset, tumor number and severity.  The F2 population (n=600) resulted from a cross between the polygenic obesity model M16i and FVB/NJ-TgN (MMTV-PyMT)634Mul, which develop synchronously appearing multifocal tumors involving all of the mammary glands with more than 85% of the animals developing pulmonary metastases by 100 days of age.  At four weeks of age all F2 individuals were randomly assigned to either a high fat (45% calories from fat) or a matched normal fat (10% calories from fat) synthetic diet.  Body weights are being recorded at periodic intervals, while body composition will be analyzed at pre- and post-tumor ages using DEXA. All F2 mice will be palpated for tumors at regular intervals to determine age of onset, and will be sacrificed at 100 days of age to determine tumor number and extent of pulmonary metastasis.  Genotyping of a genome-wide panel of microsatellite markers across the F2 population will facilitate a joint QTL analysis for obesity and cancer polygenic and diet-induced phenotypes.

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