Genetic loci controlling body fat, lipoprotein metabolism, and insulin levels in a multifactorial mouse model.
Genetic loci controlling body fat, lipoprotein metabolism, and insulin levels in a multifactorial mouse model.
复制标题
多因素小鼠模型中控制体脂肪、脂蛋白代谢和胰岛素水平的基因位点。
DOI：
10.1172/jci1748
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Lusis,AJ
中科院分区：
文献类型：
--
作者：
Mehrabian,M;Wen,PZ;Fisler,J;Davis,RC;Lusis,AJ
我们分析了近交系小鼠CAST/Ei和C57 BL/6 J之间的体脂肪、瘦素水平、血浆脂蛋白水平、胰岛素水平和相关性状的遗传。CAST/Ei小鼠非常瘦，只有大约8%的体重是脂肪，而C57 BL/6 J小鼠有大约18%的体脂。使用> 200只F2小鼠的数量性状基因座分析揭示了染色体2（三个独立的基因座）和9上的高度显著的基因座（lod得分> 4.3），其有助于高脂肪饮食小鼠的小鼠脂肪垫质量。某些位点也影响血浆脂蛋白水平和胰岛素水平，无论是在食物或高脂肪饮食。体脂和脂蛋白水平的两个位点（在中央和远端2号染色体上）与对肝脂酶活性具有强烈影响的位点相吻合，肝脂酶活性与人类内脏肥胖和脂蛋白水平相关。在4号染色体上靠近瘦素受体基因的位置发现了一个与血浆瘦素水平（lod评分5.3）有关但与肥胖无关的基因座。这些数据确定了人类肥胖和糖尿病研究的候选区域和候选基因，并表明肥胖在涉及的遗传因素数量方面是高度复杂的。最后，它们支持体脂、胰岛素代谢和脂蛋白代谢之间存在特定的遗传相互作用。
We analyzed the inheritance of body fat, leptin levels, plasma lipoprotein levels, insulin levels, and related traits in an intercross between inbred mouse strains CAST/Ei and C57BL/6J. CAST/Ei mice are unusually lean, with only approximately 8% of body weight as fat, whereas C57BL/6J mice have approximately 18% body fat. Quantitative trait locus analysis using > 200 F2 mice revealed highly significant loci (lod scores > 4.3) on chromosomes 2 (three separate loci) and 9 that contribute to mouse fat-pad mass for mice on a high-fat diet. Some loci also influenced plasma lipoprotein levels and insulin levels either on chow or high-fat diets. Two loci for body fat and lipoprotein levels (on central and distal chromosome 2) coincided with a locus having strong effects on hepatic lipase activity, an activity associated with visceral obesity and lipoprotein levels in humans. A locus contributing to plasma leptin levels (lod score 5.3) but not obesity was identified on chromosome 4, near the leptin receptor gene. These data identify candidate regions and candidate genes for studies of human obesity and diabetes, and suggest obesity is highly complex in terms of the number of genetic factors involved. Finally, they support the existence of specific genetic interactions between body fat, insulin metabolism, and lipoprotein metabolism.