Suto J, Matsuura S, Imamura K, Yamanaka H, Sekikawa K
Department of Immunology, National Institute of Animal Health, Ibaraki, Japan.
Mamm Genome. 1998 Jul;9(7):506-10. doi: 10.1007/s003359900809.
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.
KK小鼠是一种多基因的非胰岛素依赖型糖尿病伴中度肥胖模型。为了确定KK小鼠体重相关的数量性状基因座(QTL),利用97个微卫星标记对192只F2代后代进行了连锁分析,这些后代来自C57BL/6J雌性与KK-A(y)(A(y)近交系)雄性的杂交,其中包括93只在刺鼠位点具有a/a基因型的小鼠和99只具有A(y)/a基因型的小鼠,从而也研究了A(y)等位基因对体重定量调节的影响。在F2代a/a小鼠中,我们在第4号染色体(Chr)上鉴定出一个QTL,在第15号和18号染色体上鉴定出两个具有提示性连锁的位点。在F2代A(y)/a小鼠中,在第6号染色体上鉴定出一个QTL,在第4号和16号染色体上鉴定出两个具有提示性连锁的位点。F2代a/a和F2代A(y)/a后代中都存在第4号染色体上的QTL,这意味着该位点可能是调节KK和KK-A(y)小鼠体重的主要成分。这些结果表明,KK小鼠的体重受多个基因控制,并且不同的基因座组合与A(y)等位基因的存在有关。第6号染色体上的QTL似乎通过控制脂肪沉积来决定体重,因为在体重和肥胖度之间鉴定出了连锁关系,并且提示该位点是由A(y)等位基因引起的肥胖代谢途径中的一个成分。