Quantitative trait loci that regulate plasma lipid concentration in hereditary obese KK and KK-A(y) mice

To identify quantitative trait loci (QTLs) responsible for regulating plasm a lipid concentration associated with obesity, linkage analysis was carried out on the 190 F-2 progeny of a cross between C57BL/6J female and KK-A(y) (A(y) allele at the agouti locus congenic) male. In F-2 a/a (agouti locus g enotype) mice, two QTLs were identified on chromosome 1 and a QTL on chromo some 3 for total-cholesterol. A QTL for HDL-cholesterol was identified on c hromosome 1 and a QTL for NEFA on chromosome 9. In F-2 A(y)/a mice, two QTL s for HDL-cholesterol were found on chromosome 1. Loci for other lipids wit h suggestive linkage were also identified. In both F-2 mice, one QTL on chr omosome 1 for total- and HDL-cholesterol was mapped near D1Mit150, in the v icinity of the apolipoprotein A-II (Apoa2) locus. Seven nucleotide substitu tions out of 309 nucleotide apolipoprotein A-II cDNA sequences were identif ied between KK and C57BL/6J. The AY allele may be an indication of the plas ma lipid levels, but its influence was less apparent than in the case of we ight control. The loci for lipids were not on identical chromosomes with th ose previously identified for obesity, suggesting that hyperlipidemia in KK does not coincidentally occur with obesity. (C) 1999 Elsevier Science B.V. All rights reserved.