Genetic loci for diet-induced atherosclerotic lesions and plasma lipids in mice
Genetic loci for diet-induced atherosclerotic lesions and plasma lipids in mice
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DOI：
10.1007/s00335-002-2187-2
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发表时间：
2003-07-01
期刊：
影响因子：
2.5
通讯作者：
Drake, TA
中科院分区：
文献类型：
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作者：
Colinayo, VV;Qiao, JH;Drake, TA
独立于影响血脂水平的遗传因素是人类动脉粥样硬化风险的主要因素，但其基础尚不清楚。本研究检测了16月龄雌性小鼠C56BL/6J和DBA/2J品系的血浆脂质和饮食诱导的动脉粥样硬化。从1岁开始，将亲本系（BXD - RI）和F-2后代小鼠喂食致动脉粥样硬化饮食16周。这在两个亲本株中诱导动脉粥样硬化病变形成，并伴有血浆LDL水平升高。然而，个体BXD RI菌株和BXD F-2小鼠显示出一系列动脉粥样硬化病变的形成与血浆脂质水平没有或充其量是弱相关。对BXD F-2小鼠的数量性状位点（QTL）分析发现，10号染色体（Chr）上有一个与主动脉病变大小有显著连锁（lod 4.5）的位点，与血浆脂质无关。在Chr 2、3、4、5、6、7、11和17上发现了其他与各种血脂测量有暗示或显著关联的位点。在这种交叉中，主要影响动脉粥样硬化的基因不同于控制血脂水平的基因。
Genetic factors independent of those affecting plasma lipid levels are a major contributor to risk for atherosclerosis in humans, yet the basis for these is poorly understood. This study examined plasma lipids and diet-induced atherosclerosis in 16-month-old female mice of strains C56BL/6J and DBA/2J. Mice of the parental strains, from recombinant inbred strains derived from these (BXD RI), and F-2 progeny were fed an atherogenic diet for 16 weeks, beginning at 1 year of age. This induced atherosclerotic lesion formation in both parental strains, accompanied by increased plasma LDL levels. However, individual BXD RI strains and the BXD F-2 mice demonstrated a range of atherosclerotic lesion formation that was not or at best weakly correlated with plasma lipid levels. Quantitative trait locus (QTL) analysis of the BXD F-2 mice identified a locus with significant linkage (lod 4.5) for aortic lesion size on Chromosome (Chr) 10 that was independent of plasma lipids. Other loci with suggestive or significant linkage for various plasma lipid measures were identified on Chr 2, 3, 4, 5, 6, 7, 11, and 17. In this intercross, the genes primarily influencing atherosclerosis are distinct from those controlling plasma lipid levels.