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1 Nutrition, The University of Tennessee, Knoxville, TN, USA
2 The Jackson Laboratory, Bar Harbor, ME, USA
* To whom correspondence should be addressed. E-mail: jhkim{at}utk.edu.
The TallyHo (TH) mouse strain is a polygenic model for type II diabetes with obesity. Genetic analysis in backcross progeny from a cross between F1[C57BL/6J (B6) x TH] and TH mice mapped a quantitative trait locus (QTL), named tabw2 (TallyHo associated body weight 2) to chromosome 6. The TH derived allele is associated with increased body weight. As a first step to identify the molecular basis of this obesity QTL, we have constructed a congenic line of mice on the B6 genetic background that carries a genomic region from TH mice containing tabw2. Congenic mice homozygous for tabw2 (B6.TH-tabw2/tabw2) fed a chow diet exhibit slightly, but significantly, higher body weight and body fat and plasma leptin levels compared to controls (B6.TH-+/+). This difference is exacerbated when the animals are maintained on a high fat and high sucrose (HFS) diet. The diet-induced obesity in tabw2 congenic mice is accompanied by hyperleptinemia, mild hyperinsulinemia, impaired glucose tolerance, and reduced glucose uptake in adipose tissue in response to insulin administration. Using F2 progeny fed HFS diet from an intercross of B6.TH-tabw2/+ mice, we were able to refine the map position of the tabw2 obesity susceptibility locus to a 15 cM region (95% confidence interval) extending distally from the marker D6Mit102. In summary, the tabw2 congenic mice are a new animal model for diet-induced obesity that will be valuable for the study of gene-diet interactions.
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