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Lessons from Gene Deletion of Endothelin Systems

  • Chapter
Endothelin and Its Inhibitors

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 152))

Abstract

Gene targeting approach in mice sometimes reveals unexpected aspects of biology. Before we found in 1992 that deletion of the endothelin (ET)-l gene produced embryonic anomalies, few people anticipated a developmental role for ET-1, which was commonly regarded as a potent vasoconstrictor and pressor peptide mainly produced by vascular endothelial cells (Masaki 1995; Levin 1995). At that time only a few signaling molecules had been demonstrated identified to mediate morphogenesis in vertebrates and it was hard to imagine that one peptide could have dual roles in embryogenesis and cardiovascular regulation. Indeed, ET-1 was the first vasoactive substance acting through G protein-coupled receptors shown to be involved in embryonic development. Subsequently the genes for ET-3, the two ET receptors and ET converting enzyme-1 (ECE-1) were also knocked out providing further evidence of the developmental roles of the ET system. Following these studies mutations of the ET-3 and ET-B receptor genes were identified in patients with human Hirschsprung’s disease. Thus, gene knockout studies paved the way to a new era of research not only on the ET system but also in the broader field of developmental biology and clinical science. Here we review the current knowledge of the developmental and pathogenetic roles of the ET system revealed by gene knockout studies.

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  1. H. Kurihara
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  2. Y. Kurihara
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  3. Y. Yazaki
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Editors and Affiliations

  1. Department of Cardiac, Vascular and Inflammation Research, The William Harvey Research Institute St. Barthomew’s and the Royal London School of Medicine and Dentistry, Charterhouse Square, London, EC1M 6BQ, UK

    Timothy D. Warner Ph.D

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Kurihara, H., Kurihara, Y., Yazaki, Y. (2001). Lessons from Gene Deletion of Endothelin Systems. In: Warner, T.D. (eds) Endothelin and Its Inhibitors. Handbook of Experimental Pharmacology, vol 152. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-56899-2_6

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  • DOI: https://doi.org/10.1007/978-3-642-56899-2_6

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