Quantitative Trait Loci Analysis for Plasma HDL-Cholesterol Concentrations and Atherosclerosis Susceptibility Between Inbred Mouse Strains C57BL/6J and 129S1/SvImJ

OBJECTIVE: The C57BL/6 (B6) and 129 mouse inbred strains differ markedly in plasma HDL-cholesterol concentrations and atherosclerosis susceptibility after a high-fat diet consumption. To identify loci controlling these traits, we performed quantitative trait loci (QTL) analysis. METHODS AND RESULTS: We fed a high-fat diet to 294 (B6x129S1/SvImJ)F2 females for 14 weeks, measured plasma HDL concentrations and size of aortic fatty-streak lesions, genotyped F2 females, and performed QTL analysis. HDL concentrations were affected by six loci: Hdlq14 and Hdlq15 on chromosome 1 (peaks cM 80 and cM 104, logarithm of odds LOD 5.3 and 9.7, respectively); Hdlq16 on chromosome 8 (cM 44, LOD 2.6); Hdlq17 on chromosome 9 (cM 24, LOD 2.9); Hdlq18 on chromosome 12 (cM 20, LOD 5.9); and Hdlq19 on chromosome 2 (cM 90), which interacted with Hdlq15. Atherosclerosis susceptibility was affected by five loci: Ath17 on chromosome 10 (cM 34, LOD 6.6); Ath18 on chromosome 12 (cM 16, LOD 3.7); Ath19 (chromosome 11, cM 60), which interacted with Ath18; and Ath20 (chromosome 10, cM 10), which interacted with Ath21 (chromosome 12, cM 50). CONCLUSIONS: We identified six loci for HDL and five loci for atherosclerosis susceptibility in a (B6x129S1/SvImJ)F2 intercross.