Quantitative trait locus analysis of neointimal formation in an intercross between C57BL/6 and C3H/HeJ apolipoprotein E-deficient mice.
Quantitative trait locus analysis of neointimal formation in an intercross between C57BL/6 and C3H/HeJ apolipoprotein E-deficient mice.
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DOI：
10.1161/circgenetics.108.792499
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发表时间：
2009-06
期刊：
影响因子：
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通讯作者：
Shi W
中科院分区：
文献类型：
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作者：
Yuan Z;Pei H;Roberts DJ;Zhang Z;Rowlan JS;Matsumoto AH;Shi W
近交系小鼠C57BL/6J(B6)和C3H/HeJ(C3H)在缺乏载脂蛋白E(apoE−/−)和饲喂西式饮食的情况下，在动脉损伤后的新生内膜形成方面存在显著差异。对B6.apoE−/−与C3H.apoE−/−小鼠的杂交后代进行数量性状基因座分析，以确定影响表型的遗传因素。将雌性B6.apoE−/−小鼠与雄性C3H.apoE−/−小鼠杂交产生F1，再杂交产生2 0 4只雄性F2代。10周龄时，F2s左颈总动脉内皮剥脱损伤。分别在损伤前1周和损伤后4周喂饲西式饮食，分析新生内膜病变大小、血脂和单核细胞趋化蛋白-1水平。在12号染色体上发现了一个显著的QTL，命名为Nih1(61 cM，LOD值：5.02)，在13号染色体上发现了一个可能影响病变大小的QTL(35 cM，LOD：2.67)。位于1号染色体远端的一个重要QTL解释了血浆非高密度脂蛋白胆固醇和甘油三酯水平的主要变化。在第1、2和3号染色体上检测到4个对循环MCP-1水平有提示作用的QTL。未观察到新生内膜病变大小与血脂水平或病变大小与血浆MCP-1水平之间的相关性。在B6和C3H小鼠模型中，新生内膜的形成是由遗传因素控制的，而不是那些影响血脂水平和循环MCP-1水平的基因因素。
Inbred mouse strains C57BL/6J (B6) and C3H/HeJ (C3H) exhibit marked differences in neointimal formation after arterial injury when deficient in apolipoprotein E (apoE−/−) and fed a Western diet. Quantitative trait locus (QTL) analysis was performed on an intercross between B6.apoE−/− and C3H.apoE−/− mice to determine genetic factors contributing to the phenotype. Female B6.apoE−/− mice were crossed with male C3H.apoE−/− mice to generate F1s, which were intercrossed to generate 204 male F2 progeny. At 10 weeks of age, F2s underwent endothelium denudation injury to the left common carotid artery. Mice were fed a Western diet for 1 week before and 4 weeks after injury and analyzed for neointimal lesion size, plasma lipid and MCP-1 levels. One significant QTL, named Nih1 (61cM, LOD score: 5.02), on chromosome 12 and a suggestive locus on chromosome 13 (35cM, LOD: 2.67) were identified to influence lesion size. One significant QTL on distal chromosome 1 accounted for major variations in plasma non-HDL cholesterol and triglyceride levels. Four suggestive QTLs on chromosomes 1, 2, and 3 were detected for circulating MCP-1 levels. No correlations were observed between neointimal lesion size and plasma lipid levels or between lesion size and plasma MCP-1 levels. Neointimal formation is controlled by genetic factors independent of those affecting plasma lipid levels and circulating MCP-1 levels in the B6 and C3H mouse model.