Genetics of obesity in KK mouse and effects of A(y) allele on quantitative regulation

KK mouse is known as a polygenic model for noninsulin-dependent diabetes mellitus with moderate obesity. To identify the quantitative trait loci (QTLs) responsible for the body weight in KK, linkage analysis with 97 microsatellite markers was carried out into 192 F2 progeny, comprising 93 mice with a/a genotype at agouti locus and 99 mice with A(y)/a genotype, of a cross between C57BL/6J female and KK-A(y) (A(y) congenic) male, thereby the influence of A(y) allele on the quantitative regulation of body weight was also examined. In F2 a/a mice, we identified a QTL on Chromosome (Chr) 4, and two loci with suggestive linkage on Chrs 15 and 18. In F2 A(y)/a mice, a QTL was identified on Chr 6, and two loci with suggestive linkage were identified on Chrs 4 and 16. That the QTL on Chr 4 was held in common between F2 a/a and F2 A(y)/a progenies implies that this locus may be a primary component regulating body weight in KK and KK-A(y). These results suggest that the body weight in KK is controlled by multiple genes, and the different combination of loci is involved in the presence of A(y) allele. The QTL on Chr 6 seemed to determine the body weight by controlling fat deposition, because the linkage was identified on body weight and adiposity, and is suggested to be a component involved in the metabolic pathway in obesity caused by the A(y) allele.