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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:161.)
© 2004 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

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

Naoki Ishimori; Renhua Li; Peter M. Kelmenson; Ron Korstanje; Kenneth A. Walsh; Gary A. Churchill; Kristina Forsman-Semb; Beverly Paigen

From The Jackson Laboratory (N.I., R.L., P.M.K., R. K., K.A.W., G.A.C., B.P.), Bar Harbor, ME, and AstraZeneca R&D Mölndal (K.F.S.), Mölndal, Sweden.

Correspondence to Dr. Beverly J. Paigen, The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609. E-mail bjp{at}jax.org

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.

Key Words: atherosclerosis • HDL cholesterol • inbred strain • mice • quantitative trait loci

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