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Reyes Fernandez et al. The relationship between calcium metabolism and bone during growth
DOI:10.1038/bonekey.2016.38
Reyes Fernandez et al. investigated the genetic mechanisms underlying the physiological response to dietary calcium (Ca) restriction using 51 lines of BXD recombinant inbred mice.
From the ages of 4–12 weeks, eight mice from each line were fed different diets, including basal Ca (0.5%; adequate intake) and low Ca (low intake; 0.25%). Bone mineral content, bone mineral density at the femur and calcium absorption levels were measured and were each found to be significantly affected by diet (P<0.0001) and BXD line (P<0.0001). A significant line-by-diet interaction (p 1⁄4 0.0006) was observed for Ca absorption only.
Linkage mapping, composite interval mapping and other techniques enabled the researchers to identify several quantitative trait loci (QTL) that impacted on multiple phenotypic traits, suggesting that interdependent bone-related phenotypes are regulated by gene clusters. Ext1 and deptor are novel gene candidates involved in bone regulation under the conditions of Ca stress; genes important in the regulation of Ca absorption (Dennd3, Sc4mol, Sh3rf1 and Inadl) and bone and calcium metabolism (Aadat, Tll1 and Tceanc2) were also identified.
Editor’s comment: Our understanding of the gene-by diet (GxD) interactions affecting the attainment of peak bone mass is limited, so this study is significant. The authors used the Mouse ENCODE project data, innovatively overlaying the DNase1 hypersensitive sites information from 10 mouse adult tissues with the polymorphisms within the QTL region.
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