IDENTIFICATION OF 4 CHROMOSOMAL LOCI DETERMINING OBESITY IN A MULTIFACTORIAL MOUSE MODEL

We previously described a new mouse model for multigenic obesity, desi gnated BSB. We now report the use of a complete linkage map approach t o identify loci contributing to body fat and other traits associated w ith obesity in this model, Four loci exhibiting linkage with body fat, or with the weights of four different fat depots, residing on mouse c hromosomes 6, 7, 12, and 15, were identified and confirmed by analysis of additional BSB mice, Each of the four loci differed with respect t o their effects on the percent of body fat, specific fat depots and pl asma lipoproteins, The loci exhibited allele-specific, non-additive in teractions, A locus for hepatic lipase activity was co-incident with t he body fat and total cholesterol loci on chromosome 7, providing a po ssible mechanism linking plasma lipoproteins and obesity, The chromoso me 7 locus affecting body fat, total cholesterol and hepatic lipase ac tivity was isolated in congenic strains whose donor strain regions ove rlap with the chromosome 7 BSB locus. These results provide candidate genes and candidate loci for the analysis of human obesity.