J. Lipid Res.
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A more recent version of this article appeared on January 1, 2006

Papers In Press, published online ahead of print October 27, 2005
J. Lipid Res., doi:10.1194/jlr.M500295-JLR200
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Submitted on July 11, 2005
Revised on October 26, 2005
Accepted on October 26, 2005

Identification of quantitative trait loci that regulate obesity and serum lipid levels in Mrl/MpJ x Sjl/j inbred mice

Apurva K. Srivastava, Subburaman Mohan, Godfred Masinde, Hongrun Yu, and David J. Baylink

Musculoskeletal Disease Center, Jerry L. Pettis Memorial VA Medical Center, Loma Linda, CA 92357

Corresponding Author: Apurva.Srivastava{at}med.va.gov

The body fat mass, serum concentration of total cholesterol, high-density lipoprotein (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 MRLxSJL F2 female mice using 132 markers. Percentage fat mass was affected by two significant loci D11Mit36 [peak centimorgan 43.7 (cM), logarithm of odds (LOD) 11.2] and D16Mit51 (50.3 cM, LOD 3.9), and one suggestive locus at D7Mit44 (50 cM, LOD 2.4). Triglyceride levels were affected by two new loci at D1Mit43 (76 cM, LOD 3.8) and D12Mit201 (26 cM, LOD 4.1), and two suggestive loci at D5Mit136 (55 cM, LOD 3.1) and D17Mit175 (30 cM, LOD 2.6). HDL and cholesterol concentrations were influenced by significant loci on Chr 1, 3, 5, 7, and 17 that were in the regions identified earlier for other strains of mice, except for a suggestive locus on Chr 14 that was specific to the MRLxSJL cross. Among various loci identified in this study, a Chr 1 locus (D1Mit453) was in close proximity of loci that regulate cholesterol and HDL levels in blood, and appears to have a pleiotropic influence on fat mass and TG levels, indicating that Chr 1 QTL may contain gene(s) that regulate multiple phenotypes related to obesity. In summary, linkage analysis in MRLxSJL F2 mice disclosed novel loci affecting triglyceride, and fat mass, a measure of obesity, and confirmed previously identified loci affecting HDL and cholesterol. Knowledge of the genes in these QTLs will enhance our understanding of obesity and lipid metabolism.


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