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  • Transgenic mice overexpressing tartrate-resistant acid phosphatase exhibit an increased rate of bone turnover

    Author(s)
    Angel, NZ
    Walsh, N
    Forwood, MR
    Ostrowski, MC
    Cassady, AI
    Hume, DA
    Griffith University Author(s)
    Cassady, Ian
    Forwood, Mark R.
    Year published
    2000
    Metadata
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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 ...
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    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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    Journal Title
    Journal of Bone and Mineral Research
    Volume
    15
    Issue
    1
    DOI
    https://doi.org/10.1359/jbmr.2000.15.1.103
    Subject
    Genome Structure and Regulation
    Cell Development, Proliferation and Death
    Biological Sciences
    Engineering
    Medical and Health Sciences
    Publication URI
    http://hdl.handle.net/10072/63042
    Collection
    • Journal articles

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