Quantitative trait loci that determine lipoprotein cholesterol levels in DBA/2J and CAST/Ei inbred mice.
Document Type
Article
Publication Date
2003
First Page
953
Last Page
967
JAX Source
J Lipid Res 2003 May; 44(5):953-67.
Abstract
To investigate genetic contributions to individual variations of lipoprotein cholesterol concentrations, we performed quantitative trait locus/loci (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 centimorgans (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, colocalized 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 that, 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, respectively, are likely primary genetic determinants of quantitative variation of lipoprotein levels in mice and, by orthology, in the human population.
Recommended Citation
Lyons MA,
Wittenburg H,
Li R,
Walsh KA,
Churchill GA,
Carey MC,
Paigen B.
Quantitative trait loci that determine lipoprotein cholesterol levels in DBA/2J and CAST/Ei inbred mice. J Lipid Res 2003 May; 44(5):953-67.