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Studies from ADAM Knockout Mice

  • Chapter
Book cover The ADAM Family of Proteases

Part of the book series: Proteases in Biology and Disease ((PBAD,volume 4))

Abstract

ADAMs are membrane anchored glycoproteins that contain a disintegrin and metalloprotease domain. This chapter will focus on recent insights that have emerged from studies of “knockout” mice for ADAM proteases that are widely expressed or at least expressed in a variety of different cells and tissues (ADAMs 8, 9, 10, 12, 15, 17 and 19). These studies have shown that ADAM10 is important for signaling via the cell surface receptor Notch during development, while ADAM17 is critical for the development of the lung, epithelial structures and semilunar heart valves because of its role in the functional activation of ligands of the epidermal growth factor receptor. ADAM19 is essential for proper development of heart valves and the ventricular septum, although the underlying mechanism remains to be established. On the other hand, ADAMs 8, 9, 12 and 15 are dispensable for normal development and adult life in mice, at least under laboratory conditions. However, ADAM15 has a critical role in pathological neovascularization, making it a potential target for the design of inhibitors of angiogenesis. The availability of viable knockout mice for several widely expressed ADAM proteases sets the stage for a more comprehensive analysis of potential functions of these proteins in physiological and pathological processes. Furthermore, in light of the essential roles of ADAMs 10, 17 and 19 in development, it will be interesting to generate conditional knockout mice in order to evaluate the function of these proteases in adult animals.

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Authors and Affiliations

  1. Arthritis and Tissue Degeneration Program and Cell Biology Program, Hospital for Special Surgery, Weil Medical College of Cornell University, New York, NY, USA

    Keisuke Hoiruchi & Carl P. Blobel

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  1. Keisuke Hoiruchi
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  2. Carl P. Blobel
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Editors and Affiliations

  1. University of Leeds, UK

    Nigel M. Hooper

  2. University of Magdeburg, Germany

    Uwe Lendeckel

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Hoiruchi, K., Blobel, C.P. (2005). Studies from ADAM Knockout Mice. In: Hooper, N.M., Lendeckel, U. (eds) The ADAM Family of Proteases. Proteases in Biology and Disease, vol 4. Springer, Boston, MA. https://doi.org/10.1007/0-387-25151-0_2

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