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Journal of Lipid Research, Vol. 47, 123-133, January 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Identification of quantitative trait loci that regulate obesity and serum lipid levels in MRL/MpJ x SJL/J inbred mice

Apurva K. Srivastava^1,*,, Subburaman Mohan^*,, Godfred L. Masinde², Hongrun Yu^* and David J. Baylink^*,

^* Musculoskeletal Disease Center, Loma Linda VA Health Care Systems, Loma Linda, CA 92357
Department of Medicine, Loma Linda University, Loma Linda, CA 92354

Published, JLR Papers in Press, October 27, 2005.

² Present address of Godfred L. Masinde: Long Beach Genetics-Esoterix, Rancho Dominguez, CA 90220.

¹ To whom correspondence should be addressed. e-mail: apurva.srivastava{at}med.va.gov

The total body fat mass and serum concentration of total cholesterol, HDL cholesterol, and triglyceride (TG) differ between standard diet-fed female inbred mouse strains MRL/MpJ (MRL) and SJL/J (SJL) by 38–120% (P < 0.01). To investigate genetic regulation of obesity and serum lipid levels, we performed a genome-wide linkage analysis in 621 MRLx SJL F₂ female mice. Fat mass was affected by two significant loci, D11Mit36 [43.7 cM, logarithm of the odds ratio (LOD) 11.2] and D16Mit51 (50.3 cM, LOD 3.9), and one suggestive locus at D7Mit44 (50 cM, LOD 2.4). TG levels were affected by two novel loci at D1Mit43 (76 cM, LOD 3.8) and D12Mit201 (26 cM, LOD 4.1), and two suggestive loci on chromosomes 5 and 17. HDL and cholesterol concentrations were influenced by significant loci on chromosomes 1, 3, 5, 7, and 17 that were in the regions identified earlier for other strains of mice, except for a suggestive locus on chromosome 14 that was specific to the MRL x SJL cross. In summary, linkage analysis in MRL x SJL F₂ mice disclosed novel loci affecting TG, HDL, and fat mass, a measure of obesity. Knowledge of the genes in these quantitative trait loci will enhance our understanding of obesity and lipid metabolism.

Supplementary key words body fat mass • HDL cholesterol • cholesterol • triglyceride

Abbreviations: apoA-II, apolipoprotein A-II; CVD, cardiovascular disease; LOD, logarithm of the odds ratio; QTL, quantitative trait locus; SNP, single-nucleotide polymorphism; TG, triglyceride

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