Mapping of obesity QTLs in a cross between mouse lines divergently selected on fat content

A genome-wide quantitative trait locus (QTL) analysis was performed in a po lygenic obesity mouse model resulting from a long-term selection experiment . The parental lines were outbred lines divergently selected for 53 generat ions for high-fat (fat, F line) or low-fat (lean, L line) percentage (fat%) that differed fivefold in fat% at 14 weeks of age. Pin Fz population of 43 6 mice was used for the QTL analysis with 71 markers distributed across the genome. The analysis revealed significant QTLs Fob1 (for F-line obesity QT L 1), Fob2, Fob3, and Fob4 on Chromosomes (Chrs) 2, 12, 15, and X, respecti vely. None of these QTLs map to regions of known single gene obesity mutati ons (Lep(ob), Lepr(db), Cpd(fat): A(y), tub), though they map to regions of previously described obesity QTLs and candidate genes. The effects of Fob1 , Fob3, Fob4 were additive, and that of FobZ was dominant. Fob2 also showed a significant female-specific effect. Fob1, FobZ, Fob3, and Fob4 explained 4.9%, 19.5%, 14.3%, and 7.3% of the F, phenotypic variance for fat%, respe ctively. This study identified four loci that contributed to the response t o divergent selection and control a significant proportion of the differenc e in obesity between the F and L lines.