Genetic analysis of diet-induced hypercholesterolemia in exogenously hypercholesterolemic rats
Genetic analysis of diet-induced hypercholesterolemia in exogenously hypercholesterolemic rats
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DOI：
10.1194/jlr.m500257-jlr200
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发表时间：
2005-10-01
影响因子：
6.5
通讯作者：
Imaizumi, K
中科院分区：
文献类型：
--
作者：
Asahina, M;Sato, M;Imaizumi, K
外源性高胆固醇血症大鼠是一种已建立的品系，在喂食含胆固醇的食物后表现出高胆固醇血症的多基因综合征，这种综合征的程度在雄性和雌性大鼠之间存在差异。本研究旨在探讨食源性高胆固醇血症大鼠的遗传背景。利用数量性状基因座(QTL)对ExHC大鼠和Brown-挪威大鼠F2代进行了分析。给大鼠喂食含有1%胆固醇的食物，然后进行全基因组扫描。在标记D5Rat95和D14Rat43附近的第5和14号染色体上发现了对血清总胆固醇水平有显著影响的QTL，其优势分数的最大对数分别为6.0和5.8。在第3染色体上的D3Rat140上也检测到一个与该性状有关的暗示QTL。特别是5号染色体上的QTL是雌性大鼠所特有的。这些基因座是影响饮食后血清总胆固醇水平的新QTL。此外，F1代的交叉交配分析表明，ExHC大鼠对饮食胆固醇的反应部分归因于X连锁遗传。确定这样的遗传因素可能有助于预测与饮食诱导的人类高胆固醇血症相关的风险。
The exogenously hypercholesterolemic (ExHC) rat is an established strain that exhibits a polygenic syndrome of hypercholesterolemia after feeding on a cholesterol-containing diet, and the extent of this differs between male and female rats in the strain. The present study was performed to determine the genetic background of diet- induced hypercholesterolemia in ExHC rats. We used quantitative trait locus (QTL) analyses of the F2 progeny derived from ExHC and Brown-Norway rats. Rats were fed a diet containing 1% cholesterol, and a genome-wide scan was then performed. Significant QTLs for serum total cholesterol levels were revealed on chromosomes 5 and 14 in the vicinity of markers D5Rat95 and D14Rat43, having maximum logarithm of the odds scores of 6.0 and 5.8, respectively. A suggestive QTL for the trait was also detected on chromosome 3 at D3Rat140. In particular, the QTL on chromosome 5 was specific for female rats. These loci were novel QTLs for postdietary serum total cholesterol levels. In addition, cross-mating analysis in F1 generations suggested that the responsiveness to dietary cholesterol in ExHC rats is partly attributable to X-linked inheritance. Identifying such genetic factors may be useful in predicting the risks associated with diet-induced hypercholesterolemia in humans.