Transgenic Mice Overexpressing Tartrate-Resistant Acid Phosphatase Exhibit an Increased Rate of Bone Turnover

Authors

  • Nicola Z. Angel,

    1. Centre for Molecular and Cellular Biology and Departments of Biochemistry and Microbiology and Parasitology, University of Queensland, St. Lucia, Queensland, Australia
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  • Nicole Walsh,

    1. Centre for Molecular and Cellular Biology and Departments of Biochemistry and Microbiology and Parasitology, University of Queensland, St. Lucia, Queensland, Australia
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  • Mark R. Forwood,

    1. Department of Anatomical Sciences, University of Queensland, St. Lucia, Queensland, Australia
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  • Michael C. Ostrowski,

    1. Department of Molecular Genetics, Ohio State University, Columbus, Ohio, U.S.A.
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  • A. Ian Cassady,

    1. Centre for Molecular and Cellular Biology and Departments of Biochemistry and Microbiology and Parasitology, University of Queensland, St. Lucia, Queensland, Australia
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  • David A. Hume

    Corresponding author
    1. Centre for Molecular and Cellular Biology and Departments of Biochemistry and Microbiology and Parasitology, University of Queensland, St. Lucia, Queensland, Australia
    • Address reprint requests to: D. A. Hume Department of Microbiology and Paresitology University of Queensland St. Lucia, Queensland 4072, Australia
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Abstract

Tartrate-resistant acid phosphatase (TRAP) is a secreted product of osteoclasts and a lysosomal hydrolase of some tissue macrophages. To determine whether TRAP expression is rate-limiting in bone resorption, we overexpressed TRAP in transgenic mice by introducing additional copies of the TRAP gene that contained the SV40 enhancer. In multiple independent mouse lines, the transgene gave a copy number–dependent increase in TRAP mRNA levels and TRAP activity in osteoclasts, macrophages, serum, and other sites of normal low-level expression (notably, liver parenchymal cells, kidney mesangial cells, and pancreatic secretory acinar cells). Transgenic mice had decreased trabecular bone consistent with mild osteoporosis. Measurements of the bone formation rate suggest that the animals compensate for the increased resorption by increasing bone synthesis, which partly ameliorates the phenotype. These mice provide evidence that inclusion of an irrelevant enhancer does not necessarily override a tissue-specific promoter.

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