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

N Z Angel, N Walsh, M R Forwood, M C Ostrowski, A I Cassady, D A Hume

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)103-10
Number of pages8
JournalJournal of Bone and Mineral Research
Volume15
Issue number1
DOIs
Publication statusPublished - Jan 2000

Keywords

  • Acid Phosphatase
  • Animals
  • Bone Resorption
  • Cells, Cultured
  • Isoenzymes
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Osteoclasts
  • Promoter Regions, Genetic
  • RNA, Messenger

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