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J. Lipid Res.
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A more recent version of this article appeared on October 1, 2005

Papers In Press, published online ahead of print August 1, 2005
J. Lipid Res., doi:10.1194/jlr.M500257-JLR200
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Submitted on June 20, 2005
Revised on July 22, 2005
Accepted on July 27, 2005

Genetic analysis of diet-induced hypercholesterolemia in exogenously hypercholesterolemic (ExHC) rats

Makoto Asahina, Masao Sato, and Katsumi Imaizumi

Department of Agriculture, Kyushu University, Fukuoka 812-8581

Corresponding Author: imaizumi{at}agr.kyushu-u.ac.jp

Exogenously hypercholesterolemic (ExHC) rats are 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 employed 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 odds (LOD) 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 post-dietary serum total cholesterol levels. In addition, the cross-mating analysis in F1 generations suggested that the responsiveness to dietary cholesterol in ExHC rats is partly due to X-linked inheritance. Identifying such genetic factors may be useful in predicting the risks associated with diet-induced hypercholesterolemia in humans.


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