Taylor B A, Tarantino L M, Phillips S J
The Jackson Laboratory, Bar Harbor, Maine 04609-1500, USA.
Mamm Genome. 1999 Oct;10(10):963-8. doi: 10.1007/s003359901141.
The inheritance of adiposity and related traits has been investigated in the obese, diabetes-prone KK/HlLt (KK) and the lean, normoglycemic C57BL/6J (B6) mouse strains, their F(1) hybrids, and a large intercross generation. Adiposity index (AI) was defined as the sum of four fat depot weights divided by body weight. Both male and female KK mice were obese, but AI values averaged twofold higher in females than in males. In contrast, B6 females were slightly more lean than males. A genome-wide search revealed several qualitative trait loci (QTLs) affecting AI. The proximal region of Chromosome (Chr) 9 has a large effect on AI, with a much stronger effect in females (lod = 6.3) than in males (lod = 2.7). The data for females fit a model in which a dominant allele from KK increases AI by 30%, with the lod score peak falling between markers D9Mit66 and D9Mit328. This QTL has large effects on inguinal and mesenteric fat pad weights, with smaller effects on gonadal and retroperitoneal fat pads. The region of Chr 9 containing this QTL has extensive homology to human Chr 11q. An X-linked QTL affecting AI was evident in males (lod = 3.77), but not females (lod = 0.7). Exclusion of mesenteric fat from male AI resulted in an increased lod score (lod = 5.0) at 8 cM distal to DXMit166. A suggestive AI QTL (lod = 4.2), differentially affecting males, was localized to Chr 18 near the glucocorticoid receptor locus. A region of Chr 7 had a strong effect on body weight (lod = 6.9), a significant effect on inguinal fat% (lod = 4.4), and a suggestive effect on AI in females (lod = 4.1). Plasma leptin levels were associated with genotypes on Chr 9 (lod = 5.9) and Chr 7 (lod = 4.2). A region of Chr 1 had a suggestive effect on fasted blood glucose (lod = 3.6).
在肥胖、易患糖尿病的KK/HlLt（KK）小鼠品系和瘦型、血糖正常的C57BL/6J（B6）小鼠品系、它们的F(1)杂种以及一个大的杂交后代中，对肥胖及相关性状的遗传进行了研究。肥胖指数（AI）定义为四个脂肪储存重量之和除以体重。雄性和雌性KK小鼠均肥胖，但雌性的AI值平均比雄性高两倍。相比之下，B6雌性小鼠比雄性略瘦。全基因组搜索揭示了几个影响AI的质量性状位点（QTL）。9号染色体（Chr）的近端区域对AI有很大影响，在雌性中（lod = 6.3）的影响比在雄性中（lod = 2.7）更强。雌性的数据符合一个模型，即来自KK的显性等位基因使AI增加30%，lod分数峰值落在标记D9Mit66和D9Mit328之间。这个QTL对腹股沟和肠系膜脂肪垫重量有很大影响，对性腺和腹膜后脂肪垫的影响较小。包含这个QTL的9号染色体区域与人类11号染色体q臂有广泛的同源性。一个影响AI的X连锁QTL在雄性中很明显（lod = 3.77），但在雌性中不明显（lod = 0.7）。从雄性AI中排除肠系膜脂肪后，在DXMit166远端8 cM处的lod分数增加（lod = 5.0）。一个提示性的AI QTL（lod = 4.2），对雄性有不同影响，定位于靠近糖皮质激素受体基因座处的18号染色体。7号染色体的一个区域对体重有很大影响（lod = 6.9），对腹股沟脂肪百分比有显著影响（lod = 4.4），对雌性的AI有提示性影响（lod = 4.1）。血浆瘦素水平与9号染色体（lod = 5.9）和7号染色体（lod = 4.2）上的基因型相关。1号染色体的一个区域对空腹血糖有提示性影响（lod = 3.6）。
