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Related Experiment Videos

Tartrate-resistant acid phosphatase knockout mice.

Alison R Hayman1, Timothy M Cox

  • 1Department of Clinical Veterinary Science, University of Bristol, Langford, United Kingdom.

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
|October 31, 2003
PubMed
Summary

Targeting tartrate-resistant acid phosphatase (TRACP) disrupts skeletal development and impairs macrophage function. TRACP knockout mice exhibit bone deformities and delayed pathogen clearance, highlighting its role in immunity and bone remodeling.

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Area of Science:

  • Biochemistry
  • Immunology
  • Skeletal Biology

Background:

  • Tartrate-resistant acid phosphatase (TRACP) is a lysosomal enzyme present in osteoclasts, macrophages, and dendritic cells.
  • Its precise in vivo function, particularly in skeletal and immune processes, remains incompletely understood.

Purpose of the Study:

  • To elucidate the in vivo role of TRACP in skeletal development and macrophage function.
  • To investigate the interplay between TRACP, lysosomal acid phosphatase (LAP), and osteopontin.

Main Methods:

  • Generation of TRACP-deficient mice using targeted homologous recombination in embryonic stem cells.
  • Phenotypic analysis of TRACP knockout mice, including skeletal morphology, bone mineralization, and macrophage function assays.
  • Assessment of immune responses, cytokine profiles, and microbial pathogen clearance.

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  • Cross-breeding TRACP knockout mice with LAP-deficient mice.

    • Main Results:

    • TRACP knockout mice displayed progressive skeletal deformities, including foreshortened long bones and axial skeleton, indicative of impaired endochondral ossification.
    • Mild osteopetrosis was observed due to reduced osteoclast modeling activity and increased mineralization.
    • Macrophages lacking TRACP showed enhanced superoxide and nitrite production, increased pro-inflammatory cytokine secretion (TNF-alpha, IL-1beta, IL-12), and impaired clearance of Staphylococcus aureus.
    • Mice lacking both TRACP and LAP exhibited more severe skeletal defects than TRACP single knockouts, with accumulation of osteopontin near osteoclasts.

    Conclusions:

    • TRACP is crucial for normal skeletal development, specifically endochondral ossification and osteoclast modeling.
    • TRACP plays a significant role in macrophage function, influencing cytokine responses and pathogen clearance.
    • TRACP, along with LAP, is important for osteopontin processing, suggesting a shared regulatory role in both skeletal and immune systems.