Abstract
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.
Highlights
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)
Serum concentrations of cholesterol and HDL were higher in MRL mice by 82% (P, 0.001), and 120% (P, 0.001), respectively, as compared with SJL mice (Table 1)
The genome-wide scans of MRL 3 SJL F2 mice for associations between marker genotypes and the quantitative phenotypes of total body fat mass and serum lipid levels resulted in the localization of several novel quantitative trait locus (QTL), for percent fat mass and TG levels
Summary
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 MRL3 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 D16Mit (50.3 cM, LOD 3.9), and one suggestive locus at D7Mit (50 cM, LOD 2.4). 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 3 SJL cross. Linkage analysis in MRL 3 SJL F2 mice disclosed novel loci affecting TG, HDL, and fat mass, a measure of obesity. Identification of quantitative trait loci that regulate obesity and serum lipid levels in MRL/MpJ 3 SJL/J inbred mice.
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