Quantitative Trait Loci that Control Plasma Lipid Levels in an F₂ Intercross between C57BL/6J and DDD.Cg-<i>A^y</i> Inbred Mouse Strains

Abstract

ABSTRACT. The objectives of this study were to characterize plasma lipid phenotypes and dissect the genetic basis of plasma lipid levels in an obese DDD.Cg-A y mouse strain. Plasma triglyceride (TG) levels were significantly higher in the DDD.Cg-A y strain than in the B6.Cg-A y strain. In contrast, plasma total-cholesterol (CHO) levels did not substantially differ between the two strains. As a rule, the A y allele significantly increased TG levels, but did not increase CHO levels. Quantitative trait locus (QTL) analyses for plasma TG and CHO levels were performed in two types of F 2 female mice [F 2 A y (F 2 mice carrying the A y allele) and F 2 non-A y mice (F 2 mice without the A y allele)] produced by crossing C57BL/6J females and DDD.Cg-A y males. Single QTL scan identified one significant QTL for TG levels on chromosome 1, and two significant QTLs for CHO levels on chromosomes 1 and 8. When the marker nearest to the QTL on chromosome 1 was used as covariates, four additional significant QTLs for CHO levels were identified on chromosomes 5, 6, and 17 (two loci). In contrast, consideration of the agouti locus genotype as covariates did not detect additional QTLs. DDD.Cg-A y showed a low CHO level, although it had Apoa2 b , which was a CHO-increasing allele at the Apoa2 locus. This may have been partly due to the presence of multiple QTLs, which were associated with decreased CHO levels, on chromosome 8. KEY WORDS: cholesterol, mice, plasma lipid levels, quantitative trait locus (QTL), triglyceride.

Identification of Quantitative Trait Loci That Determine Plasma Total-Cholesterol and Triglyceride Concentrations in DDD/Sgn and C57BL/6J Inbred Mice

“…For CHO (Figure 1(b), solid lines), we identified three significant QTL on Chr 1@80.5 cM (Choldq1) , Chr 17@35.1 cM (Choldq6) , and Chr 19@8.0 cM (Choldq7) and three suggestive QTL on Chr 3@23.8 cM, Chr 5@59.8 cM, and Chr 9@37.0 cM (Table 2). The suggestive QTL on Chr 5 coincided with Choldq4 , which was previously identified as a significant QTL in C57BL/6J × DDD.Cg- A y F 2 female populations [9]; therefore, we assigned the same gene symbol Choldq4 to this QTL. For TG (Figure 2(b), solid lines), we identified one significant QTL on Chr 1@84.5 cM (Trigdq1) and four suggestive QTL on Chr 5@50.8 cM, Chr 12@47.0 cM, Chr 14@60.3 cM, and Chr 15@53.9 cM (Table 2).…”

“…Finally, we combined the data from this study on males with the previously analyzed data on B6 × DDD.Cg- A y F 2 females [9] and performed QTL mapping analysis. This analysis first aimed to increase the power of QTL mapping, as there was a possibility that we could identify additional and/or novel QTL and that the 95% CI for QTL could be narrowed by increasing the sample size.…”

“…We identified several significant QTL for plasma CHO and TG concentrations in C57BL/6J × DDD.Cg- A y F 2 female mice [9]. In the present study, we performed QTL mapping for plasma CHO and TG concentrations in F 2 male mice produced via crosses between C57BL/6J and DDD/Sgn mice.…”

“…We previously performed QTL mapping studies to identify plasma lipid concentrations using mouse intercrosses [6–9]. We identified several significant QTL for plasma CHO and TG concentrations in C57BL/6J × DDD.Cg- A y F 2 female mice [9].…”

“…Because male intercross population produced by these strains is not previously evaluated for plasma lipid concentrations, we expect novel QTL in addition to known QTL for plasma lipid concentrations to be identified. Furthermore, because there were apparent sex differences in plasma lipid concentrations between these mouse strains (e.g., female DDD.Cg- A y mice had higher TG concentrations than males, whereas male C57BL/6J mice had higher TG concentrations than females [9]), we expect genetic aspects of sex differences to be revealed. Because men have a higher risk of coronary artery disease than women [10], it is crucially important to unravel the molecular basis of sex differences in plasma lipid concentrations.…”