Quantitative trait loci that determine plasma insulin levels in $\hbox {F}_{2}$ intercross populations produced from crosses between DDD/Sgn and C57BL/6J inbred mice

Abstract

When compared to C57BL/6J (B6) mice, DDD/Sgn (DDD) mice has substantially higher plasma insulin levels in both sexes. In this study, we performed quantitative trait loci (QTL) mapping of plasma insulin levels in $\hbox {F}_{2}$ male mice produced by crosses between DDD and B6 mice. By single-QTL scans, we identified one significant QTL on chromosome 9. When body weight was included as an additive covariate, we identified two significant QTL on chromosomes 9 and 12; the latter coincided with a QTL that was previously identified in $\hbox {F}_{2}$ female mice produced by the same two strains. The inheritance mode and the direction of the allelic effect of QTL on chromosome 12 were similar in both sexes, but those on chromosome 9 differed between males and females, suggesting that the QTL on chromosome 9 was sex-specific. Based on phenotypic correlations of plasma insulin levels with body weight and plasma levels of total cholesterol, triglyceride and testosterone, we subsequently assessed whether these insulin QTL explain the variation in other metabolic traits by using a point-wise significance threshold of $P = 0.05$. QTL on chromosome 12 had no significant effect on any trait. In contrast, QTL on chromosome 9 had significant effects on body weight and total cholesterol level. We postulate that Gpr68 and Cyp19a1 are plausible candidate genes for QTL on chromosomes 12 and 9, respectively. These findings provide insight into the genetic mechanisms underlying insulin metabolism.