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J. Lipid Res.
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A more recent version of this article appeared on May 1, 2003

Papers In Press, published online ahead of print February 16, 2003
J. Lipid Res., doi:10.1194/jlr.M300002-JLR200
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Submitted on January 2, 2003
Revised on February 10, 2003
Accepted on February 11, 2003

Quantitative trait loci that determine lipoprotein cholesterol levels in DBA/2J and CAST/Ei inbred mice

Malcolm A. Lyons, Henning Wittenburg, Renhua Li, Kenneth A. Walsh, Gary A. Churchill, Martin C. Carey, and Beverly Paigen

The Jackson Laboratory, Bar Harbor, ME 04609

Corresponding Author: bjp{at}jax.org

To investigate genetic contributions to individual variations of lipoprotein cholesterol concentrations, we performed quantitative trait locus (QTL) analyses of an intercross of CAST/Ei and DBA/2J inbred mouse strains after feeding a high-cholesterol, cholic acid diet for 10 weeks. In total, we identified four QTL for HDL cholesterol. Three of these were novel and were named Hdlq10 (20 cM, chromosome 4), Hdlq11 (48 cM, chromosome 6) and Hdlq12 (68 cM, chromosome 6). The fourth QTL, Hdl1 (48 cM, chromosome 2), confirmed a locus discovered previously using a breeding cross that employed different inbred mouse strains. In addition, we identified one novel QTL for total and non-HDL cholesterol (8 cM, chromosome 9) that we named Chol6. Hdlq10 co-localized with a mutagenesis-induced point mutation (Lch) also affecting HDL. We provide molecular evidence for Abca1 as the gene underlying Hdlq10 and Ldlr as the gene underlying Chol6, which, coupled with evidence generated by other researchers using knockout and transgenic models, causes us to postulate that polymorphisms of these genes, different from the mutations leading to Tangier’s Disease and Familial Hypercholesterolemia, are likely primary genetic determinants of quantitative variation of lipoprotein levels in mice and, by orthology, in the human population.


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