Quantitative trait locus on chromosome X affects bone loss after maturation in mice.

Genetic programming is known to affect the peak bone mass and bone loss after maturation. However, little is known about how polymorphic genes on chromosome X (Chr X) modulate bone loss after maturation. We previously reported a quantitative trait locus (QTL) on Chr X, designated Pbd3, which had a suggestive linkage to bone mass, in male SAMP2 and SAMP6 mice. In this study, we aimed to clarify the effects of Pbd3 on the skeletal phenotype. We generated a congenic strain, P2.P6-X, carrying a 45.6-cM SAMP6-derived Chr X interval on a SAMP2 genetic background. The effects of Pbd3 on the bone phenotype were determined by microcomputed tomography (microCT), whole-body dual-energy X-ray absorptiometry (DXA), serum bone turnover markers, and histomorphometric parameters. Both the bone area fraction (BA/TA) on microCT and whole-body DXA revealed reduced bone loss in P2.P6-X compared with that in SAMP2. The serum concentrations of bone turnover markers at 4 months of age were significantly lower in P2.P6-X than in SAMP2, but did not differ at 8 months of age. These results were observed in female mice, but not in male mice. In conclusion, a QTL within a segregated 45.6-cM interval on Chr X is sex-specifically related to the rate of bone loss after maturation.