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Cancer and Metastasis Reviews

, Volume 14, Issue 2, pp 97–111 | Cite as

Utilization of transgenic mice in the study of matrix degrading proteinases and their inhibitors

  • Rama Khokha
  • David C. Martin
  • Jimmie E. Fata
Article

Abstract

The extracellular matrix (ECM) acts as both a structural scaffold and an informational medium. Its dynamic status is determined by cells that secrete its constituent molecules and, in most cases, also secrete enzymes that catalyze degradation of these molecules. A stasis between ECM degrading enzymes and their inhibitors maintains the integrity of the matrix. While controlled ECM remodelling is fundamental to several normal processes, uncontrolled disruption underlies diverse pathological conditions. Transgenic mice with specific modulations or a total lack of expression of certain metalloproteinases, serine proteinases or their inhibitors have been generated to elucidate endogenous expression patterns, identify regulatory elements of these genes, and study the physiological consequences of their deregulated expression. With these models we enhance our understanding of the role of proteinases and their inhibitors in diverse normal processes and pathologies including mammary gland development, hemostasis, emphysema and cancer.

Key words

metalloproteinases serine proteinases proteinase inhibitors extracellular matrix transgenic mice 

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Copyright information

© Kluwer Academic Publishers 1995

Authors and Affiliations

  • Rama Khokha
    • 1
  • David C. Martin
    • 1
  • Jimmie E. Fata
    • 1
  1. 1.Departments of Oncology and BiochemistryUniversity of Western Ontario, London Regional Cancer CentreLondon, OntarioCanada

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