Quantitative trait locus mapping of genes that regulate HDL cholesterol in SM/J and NZB/B1NJ inbred mice

1 The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609 2 GlaxoWellcome, Laboratoire Glaxo Wellcome, Centre de Recherches, 91951 Les Ulis Cedex, France 3 Department of Medicine, Northwest Lipid Research Laboratories, University of Washington, Seattle, Washington 98103 4 GlaxoWellcome, Molecular Pathology, Medicines Research Centre, Stevenage, United Kingdom To investigate the quantitative trait loci (QTL) regulating plasma cholesterol, the female progeny of an (SM x NZB/ B1NJ) x NZB/B1NJ backcross were fed an atherogenic diet. After 18 wk, plasma total cholesterol and high-density lipoprotein cholesterol (HDL-C) was measured. HDL-C concentrations were greater in NZB than in SM mice. For standard chow-fed mice, QTL were found near D5Mit370 and D18Mit34 . For mice fed an atherogenic diet, a QTL was found near D5Mit239 . The QTL for chow-fed and atherogenic-fed mice on chromosome 5 seem to be two different loci. We used a multitrait analysis to rule out pleiotropy in favor of a two-QTL hypothesis. Furthermore, the HDL-C in these strains was induced by the high-fat diet. For inducible HDL-C, one significant locus was found near D15Mit39 . The gene for an HDL receptor, Srb1 , maps close to the HDL-C QTL at D5Mit370 , but the concentrations of Srb1 mRNA and SR-B1 protein and the gene sequence of NZB/B1NJ and SM/J did not support Srb1 as a candidate gene. With these QTL, we have identified chromosomal regions that affect lipoprotein profiles in these strains. high-density lipoprotein; cholesterol; genetics; Srb1