Identification of genetic loci controlling intestinal calcium (Ca) absorption using BXD recombinant inbred (RI) mice fed high or low dietary Ca

Abstract

Intestinal Ca absorption (Ca Abs) is affected by race and is similar between mothers and daughters suggesting genetic regulation of this trait. However, the impact of genetics on CaAbs and the adaptation of Ca Abs to inadequate dietary Ca intake is not known. We examined the role of genetics on Ca Abs efficiency in 51 lines of BXD RI mice. Mice were fed AIN93G diets with either 0.5% or 0.25% Ca from 4 to 12 wks of age (n=8/line/diet). Afterwards, Ca Abs was measured by Ca45 appearance in the blood 10 min after an oral gavage of 0.1 mM Ca. After correcting for covariates, considerable diversity was observed between the lines in Ca Abs on each diet. Narrow‐sense heritability for Ca Abs was 0.37 and 0.56 in the 0.5% and 0.25% Ca diets, respectively, demonstrating increased penetrance of genetic effects controlling Ca Abs with low Ca diets. Linkage mapping was conducted using both traditional and Bayesian methods. Quantitative trait loci (QTL) affecting Ca Abs were identified that were diet‐specific (0.25%: on Chr 5, 8 (distal), 9, 12, 17; 0.5% on Chr 8 (proximal), 10) and shared (Chr 4, 7). No known Ca regulatory genes were found around these QTL demonstrating the potential of this approach for discovery of new genes controlling Ca Abs. This study provides a foundation for determining genetic regulators that may underlie individual differences in Ca Abs and ultimately dietary Ca requirements. Supported by NIEHS award ES019103.Grant Funding Source : NIEHS