A congenic mouse and candidate gene at the Chromosome 13 locus regulating bone density.
Previously, we identified two significant quantitative trait loci (QTLs) specifying the peak relative bone mass (bone mass corrected for bone size) on chromosomes (Chrs) 11 and 13 by interval mapping in two mouse strains, SAMP2 and SAMP6. The latter strain is an established murine model of senile osteoporosis and exhibits a significantly lower peak relative bone mass than SAMP2 mice. We recently designated the Chr 13 locus as Pbd2 (Peak bone density 2) and constructed a congenic strain, P6.P2-Pbd2(b), which carried a single genomic interval from the Chr 13 of SAMP2 on a SAMP6-derived osteoporotic background. In this study, we have constructed a congenic strain, P2.P6-Pbd2(a), carrying a SAMP6-derived susceptible interval on a SAMP2-derived resistance background. This congenic strain had a lower bone density than the background strain, SAMP2, based on three measurement methods, each utilizing a different principle for evaluating bone density: MD, DXA, and pQCT. Next, a candidate gene approach was used to find polymorphisms of Bmp6 (bone morphogenetic protein 6). The CAG trinucleotide repeat numbers in exon 1 of this gene differ among SAM strains. We found an association of CAG repeat length with relative peak bone mass in mice.
Shimizu
Motoyuki
M
Department of Orthopaedic Surgery, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Higuchi
Keiichi
K
Kasai
Soichiro
S
Tsuboyama
Tadao
T
Matsushita
Mutsumi
M
Matsumura
Takuro
T
Okudaira
Shuzo
S
Mori
Masayuki
M
Koizumi
Akio
A
Nakamura
Takashi
T
Hosokawa
Masanori
M
D000818:Animals; D001483:Base Sequence; D015519:Bone Density / Q000235:genetics*; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000235:genetics*; D005269:Femur / Q000033:anatomy & histology; D051379:Mice; D020297:Mice, Congenic; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009929:Organ Size; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics*; D018911:Trinucleotide Repeats / Q000235:genetics