Chromosome 13 Locus, Pbd2, Regulates Bone Density in Mice

Authors

  • Motoyuki Shimizu,

    1. Department of Orthopedic Surgery, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan
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  • Keiichi Higuchi,

    1. Department of Aging Angiology, Research Center for Aging and Adaptation, Shinshu University School of Medicine, Matsumoto, Japan
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  • Soichiro Kasai,

    1. Department of Orthopedic Surgery, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan
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  • Tadao Tsuboyama,

    1. Division of Physical Therapy, College of Medical Technology, Kyoto University, Sakyo-ku, Kyoto, Japan
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  • Mutsumi Matsushita,

    1. Department of Orthopedic Surgery, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan
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  • Masayuki Mori,

    1. Department of Aging Angiology, Research Center for Aging and Adaptation, Shinshu University School of Medicine, Matsumoto, Japan
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  • Yasuhiko Shimizu,

    1. Department of Bioartificial Organs, Field of Clinical Application, Institute for Frontier Medical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan
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  • Takashi Nakamura,

    1. Department of Orthopedic Surgery, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan
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  • Masanori Hosokawa

    Corresponding author
    1. Field of Regeneration Control, Institute for Frontier Medical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan
    • Address reprint requests to: Masanori Hosokawa, M.D., Ph.D., Field of Regeneration Control, Institute for Frontier Medical Sciences, Kyoto University, Kawahara-cho 53, Shogoin, Sakyo-ku, Kyoto 606–8507, Japan
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Abstract

Bone density is inherited as a complex polygenic trait. Previously, we identified two quantitative trait loci (QTLs) specifying the peak relative bone mass (bone mass corrected by 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. In this study, we report the effects of the Chr 13 QTL on peak bone density (Pbd2). First, we constructed a congenic strain P6.P2-Pbd2b, which carried a single genomic interval from the Chr 13 of SAMP2 on an SAMP6-derived osteoporotic background, to dissect this polygenic trait into single gene factors. This congenic strain had a higher bone density than the background strain using three measurement methods with different principles for bone density. Next, we measured the peak relative bone mass of the AKR/J strain and the 13 senescence-accelerated mouse (SAM) strains, which are considered to be a series of recombinant-like inbred (RI) strains derived from the AKR/J strain and other unspecified strains. We then determined the microsatellite marker haplotypes of these strains around the Pbd2 locus, in which three strains with a high relative bone mass shared the same haplotype over the 26-centimorgan (cM) region. In the Pbd2 locus, a high relative bone mass was associated with alleles of the unknown strain, whereas a low relative bone mass was associated with the alleles from the AKR/J strain. These results confirmed the existence of a Pbd2 locus regulating bone density in the SAM strains.

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