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Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:2072-2079
Published online before print October 3, 2002, doi: 10.1161/01.ATV.0000040225.16592.CE
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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:2072.)
© 2002 American Heart Association, Inc.

Lipoproteins

Quantitative Trait Loci Influencing Blood and Liver Cholesterol Concentration in Rats

Anita C.M. Bonné; Maria G. den Bieman; Gert F. Gillissen; Ægidius Lankhorst; Christopher J. Kenyon; Bert F.M. van Zutphen; Hein A. van Lith

From the Department of Laboratory Animal Science, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands, and the Molecular Medicine Centre (C.J.K.), Western General Hospital, Edinburgh, UK.

Correspondence to Anita Bonné, PhD, Department of Human Genetics, UMC, St Radboud Postbus 9101, 6500 HB Nijmegen, the Netherlands. E-mail a.bonne{at}antrg.azn.nl

Abstract

Objective— The LEW/OlaHsd and BC/CpbU rat inbred strains differ markedly in blood and hepatic cholesterol levels before and after a cholesterol-rich diet. To define loci controlling these traits and related phenotypes, an F2 population derived from these strains was genetically analyzed.

Methods and Results— For each of the 192 F2 animals, phenotypes were determined, and genomic DNA was screened for polymorphic microsatellite markers. Significant quantitative trait loci (QTLs) were detected for basal serum cholesterol level on chromosome 1 (D1Rat335-D1Rat27: total population, lod score 9.6; females, lod score 10.3) and chromosome 7 (D7Rat69: males, lod score 4.1), for postdietary serum cholesterol level on chromosome 2 (D2Rat69: total population, lod score 4.4) and chromosome 16 (D16Rat6-D16Rat44: total population, lod score 3.3), for postdietary serum phospholipid level on chromosome 11 (D11Rat10: total population, lod score 4.1; females, lod score 3.6), and for postdietary serum aldosterone level on chromosome 1 (D1Rat14: females, lod score 3.7) and chromosome 18 (D18Rat55-D18Rat8: females, lod score 2.9). In addition, QTLs with borderline significance were found on chromosomes 3, 5 to 11, 15, and 18.

Conclusions— QTLs involved in blood and/or hepatic cholesterol concentrations (or related phenotypes) in the rat were identified. This contributes to the value of the rat as an animal model in studies researching the role of cholesterol in the pathogenesis of atherosclerosis and other cholesterol-related diseases.


Key Words: cholesterol • phospholipids • quantitative trait loci • steroid hormones • rats




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