[Animal models for bone and joint disease. Genetic analysis of low BMD in SAMP6 mice]

We performed the whole-genome scan for quantitative trait loci (QTLs) in SAMP6 mice that exhibits a significantly low peak bone mass. We found two significant loci on Chrs 11 and 13 (designated Pbd1 and Pbd2, respectively) and one suggestive locus on Chr X (designated Pbd3 ) that were linked to the bone mass. Next, we clarified that Pbd1 is related to the bone geometry, Pbd2 to the formation of bone before maturation, and Pbd3 to the bone loss after maturation. In particular, we showed that secreted frizzled-related protein 4 (Sfrp4) encoded by a gene within the Pbd2 locus on Chr 13 was responsible, at least in part, for the lower bone mineral density (BMD) in the SAMP6 mice, by inhibiting the proliferation of osteoblasts.