SENSITIVITY TO DIETARY OBESITY LINKED TO A LOCUS ON CHROMOSOME-15 IN A CAST EIXC57BL/6J F2 INTERCROSS/

Details of a new model of diet-dependent polygenic obesity are present ed. CAST/Ei (Mus m. castaneus) mice remain lean after 12 weeks on a hi gh-fat (32 kcal% fat) diet, while C57BL/6J mice become obese. The gene s responsible for the obesity segregate in an F-2 population derived f rom an intercross between CAST/Ei and C57BL/6J mice. Quantitative trai t analysis, with simple sequence length polymorphisms (SSLPs) at loci previously linked to rodent obesities, identified a quantitative trait locus (QTL) on Chromosome (Chr) 15, accounting for approximately 9% o f the variance in adiposity and 14% of the variance in mesenteric depo t size. This locus appears to be at the same location as the dietary o besity-3 (Do3) locus controlling body fat content, which was previousl y identified in an F-2 population derived from an SWR/J x AKR/J cross. This is also at the same location as the multigenic obesity-4 (Mob4) locus found in BSB mice, which display spontaneous polygenic obesity. Suggestive linkage also was found at loci close to the single gene mut ations A(y) On Chr 2 and tub on Chr 7.