Mutations in two matrix metalloproteinase genes, MMP-2 and MT1-MMP, are synthetic lethal in mice

Jun Seo Oh, Rei Takahashi, Eijiro Adachi, Shunya Kondo, Shinobu Kuratomi, Akinori Noma, David B. Alexander, Hirotoshi Motoda, Akiko Okada, Motoharu Seiki, Takeshi Itoh, Shigeyoshi Itohara, Chiaki Takahashi, Makoto Noda

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Abstract

The matrix metalloproteinase (MMP) family (≃25 members in mammals) has been implicated in extracellular matrix remodeling associated with embryonic development, cancer formation and progression, and various other physiological and pathological events. Inactivating mutations in individual matrix metalloproteinase genes in mice described so far, however, are nonlethal at least up to the first few weeks after birth, suggesting functional redundancy among MMP family members. Here, we report that mice lacking two MMPs, MMP-2 (nonmembrane type) and MT1-MMP (membrane type), die immediately after birth with respiratory failure, abnormal blood vessels, and immature muscle fibers reminiscent of central core disease. In the absence of MMP-2 and MT1-MMP, myoblast fusion in vitro is also significantly retarded. These findings suggest functional overlap in mice between the two MMPs with distinct molecular natures.

Original languageEnglish
Pages (from-to)5041-5048
Number of pages8
JournalOncogene
Volume23
Issue number29
DOIs
Publication statusPublished - 2004 Jun 24
Externally publishedYes

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Keywords

  • Angiogenesis
  • MMP-2
  • MT1-MMP
  • Myogenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Oh, J. S., Takahashi, R., Adachi, E., Kondo, S., Kuratomi, S., Noma, A., Alexander, D. B., Motoda, H., Okada, A., Seiki, M., Itoh, T., Itohara, S., Takahashi, C., & Noda, M. (2004). Mutations in two matrix metalloproteinase genes, MMP-2 and MT1-MMP, are synthetic lethal in mice. Oncogene, 23(29), 5041-5048. https://doi.org/10.1038/sj.onc.1207688