Suto J, Matsuura S, Yamanaka H, Sekikawa K
Department of Immunology, National Institute of Animal Health, Tsukuba, Ibaraki 305-0856,
Biochim Biophys Acta. 1999 Mar 30;1453(3):385-95. doi: 10.1016/s0925-4439(99)00013-7.
To identify quantitative trait loci (QTLs) responsible for regulating plasma lipid concentration associated with obesity, linkage analysis was carried out on the 190 F2 progeny of a cross between C57BL/6J female and KK-Ay (Ay allele at the agouti locus congenic) male. In F2 a/a (agouti locus genotype) mice, two QTLs were identified on chromosome 1 and a QTL on chromosome 3 for total-cholesterol. A QTL for HDL-cholesterol was identified on chromosome 1 and a QTL for NEFA on chromosome 9. In F2 Ay/a mice, two QTLs for HDL-cholesterol were found on chromosome 1. Loci for other lipids with suggestive linkage were also identified. In both F2 mice, one QTL on chromosome 1 for total- and HDL-cholesterol was mapped near D1Mit150, in the vicinity of the apolipoprotein A-II (Apoa2) locus. Seven nucleotide substitutions out of 309 nucleotide apolipoprotein A-II cDNA sequences were identified between KK and C57BL/6J. The Ay allele may be an indication of the plasma lipid levels, but its influence was less apparent than in the case of weight control. The loci for lipids were not on identical chromosomes with those previously identified for obesity, suggesting that hyperlipidemia in KK does not coincidentally occur with obesity.
为了鉴定与肥胖相关的调节血浆脂质浓度的数量性状基因座（QTL），对C57BL/6J雌性和KK-Ay（刺鼠基因座的Ay等位基因同基因）雄性杂交产生的190只F2后代进行了连锁分析。在F2代a/a（刺鼠基因座基因型）小鼠中，在1号染色体上鉴定出两个QTL，在3号染色体上鉴定出一个总胆固醇QTL。在1号染色体上鉴定出一个高密度脂蛋白胆固醇（HDL-胆固醇）QTL，在9号染色体上鉴定出一个非酯化脂肪酸（NEFA）QTL。在F2代Ay/a小鼠中，在1号染色体上发现了两个HDL-胆固醇QTL。还鉴定出了其他具有提示性连锁的脂质基因座。在两种F2代小鼠中，1号染色体上一个总胆固醇和HDL-胆固醇的QTL定位于靠近D1Mit150处，在载脂蛋白A-II（Apoa2）基因座附近。在KK和C57BL/6J之间的309个核苷酸的载脂蛋白A-II cDNA序列中鉴定出7个核苷酸替换。Ay等位基因可能是血浆脂质水平的一个指标，但其影响不如在体重控制方面那么明显。脂质基因座与先前鉴定的肥胖基因座不在同一条染色体上，这表明KK小鼠的高脂血症并非与肥胖同时发生。
