Potential role for ADAM15 in pathological neovascularization in mice

Keisuke Horiuchi, Gisela Weskamp, Lawrence Lum, Hans Peter Hammes, Hui Cai, Thomas A. Brodie, Thomas Ludwig, Riccardo Chiusaroli, Roland Baron, Klaus T. Preissner, Katia Manova, Carl P. Blobel

Research output: Contribution to journalArticle

141 Scopus citations

Abstract

ADAM15 (named for a disintegrin and metalloprotease 15, metargidin) is a membrane-anchored glycoprotein that has been implicated in cell-cell or cell-matrix interactions and in the proteolysis of molecules on the cell surface or extracellular matrix. To characterize the potential roles of ADAM15 during development and in adult mice, we analyzed its expression pattern by mRNA in situ hybridization and generated mice carrying a targeted deletion of ADAM15 (adam15-/- mice). A high level of expression of ADAM15 was found in vascular cells, the endocardium, hypertrophic cells in developing bone, and specific areas of the hippocampus and cerebellum. However, despite the pronounced expression of ADAM15 in these tissues, no major developmental defects or pathological phenotypes were evident in adam15-/- mice. The elevated levels of ADAM15 in endothelial cells prompted an evaluation of its role in neovascularization. In a mouse model for retinopathy of prematurity, adam15-/- mice had a major reduction in neovascularization compared to wild-type controls. Furthermore, the size of tumors resulting from implanted B16F0 mouse melanoma cells was significantly smaller in adam15-/- mice than in wild-type controls. Since ADAM15 does not appear to be required for developmental angiogenesis or for adult homeostasis, it may represent a novel target for the design of inhibitors of pathological neovascularization.

Original languageEnglish (US)
Pages (from-to)5614-5624
Number of pages11
JournalMolecular and Cellular Biology
Volume23
Issue number16
DOIs
Publication statusPublished - Aug 2003

    Fingerprint

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Horiuchi, K., Weskamp, G., Lum, L., Hammes, H. P., Cai, H., Brodie, T. A., ... Blobel, C. P. (2003). Potential role for ADAM15 in pathological neovascularization in mice. Molecular and Cellular Biology, 23(16), 5614-5624. https://doi.org/10.1128/MCB.23.16.5614-5624.2003