No abstract

No abstract

We previously described a new mouse model for multigenic obesity, designated BSB. We now report the use of a complete linkage map approach to identify loci contributing to body fat and other traits associated with obesity in this model. Four loci exhibiting linkage with body fat, or with the weights of four different fat depots, residing on mouse chromosomes 6, 7,12, and 15, were identified and confirmed by analysis of additional BSB mice. Each of the four loci differed with respect to their effects on the percent of body fat, specific fat depots and plasma lipoproteins. The loci exhibited allele-specific, non-additive interactions. A locus for hepatic lipase activity was co-incident with the body fat and total cholesterol loci on chromosome 7, providing a possible mechanism linking plasma lipoproteins and obesity. The chromosome 7 locus affecting body fat, total cholesterol and hepatic lipase activity was isolated in congenic strains whose donor strain regions overlap with the chromosome 7 BSB locus. These results provide candidate genes and candidate loci for the analysis of human obesity. (J. Clin. Invest. 1995Invest. . 95:1545Invest. -1552

No abstract

We analyzed the inheritance of body fat, leptin levels, plasma lipoprotein levels, insulin levels, and related traits in an intercross between inbred mouse strains CAST/Ei and C57BL/6J. CAST/Ei mice are unusually lean, with only ‫ف‬ 8% of body weight as fat, whereas C57BL/6J mice have ‫ف‬ 18% body fat. Quantitative trait locus analysis using Ͼ 200 F2 mice revealed highly significant loci (lod scores Ͼ 4.3) on chromosomes 2 (three separate loci) and 9 that contribute to mouse fat-pad mass for mice on a high-fat diet. Some loci also influenced plasma lipoprotein levels and insulin levels either on chow or high-fat diets. Two loci for body fat and lipoprotein levels (on central and distal chromosome 2) coincided with a locus having strong effects on hepatic lipase activity, an activity associated with visceral obesity and lipoprotein levels in humans. A locus contributing to plasma leptin levels (lod score 5.3) but not obesity was identified on chromosome 4, near the leptin receptor gene. These data identify candidate regions and candidate genes for studies of human obesity and diabetes, and suggest obesity is highly complex in terms of the number of genetic factors involved. Finally, they support the existence of specific genetic interactions between body fat, insulin metabolism, and lipoprotein metabolism. ( J. Clin. Invest. 1998. 101: 2485-2496.)