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Transgenic Animals in Primary Hemostasis and Thrombosis

  • Chapter
Transgenic Models in Pharmacology

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 159))

  • 130 Accesses

Abstract

Blood platelet activation at the contact of an injured vessel wall results in adhesion, shape change, aggregation and secretion, which are all tightly regulated biological processes to fulfill the main physiological function of platelets: the arrest of bleeding or primary hemostasis. The same mechanisms of activation are triggered when platelets encounter an atherosclerotic plaque rupturing or following mechanical or infectious injury of the vessel wall, resulting in arterial thrombosis or disseminated intravascular thrombosis. Knowledge of the molecular biology of hemostasis has increased considerably during the last few decades due to the accurate observation of defective hemostasis in patients exhibiting selective abnormalities in platelet surface glycoproteins involved in adhesive functions, defects of plasma adhesive proteins, or defects affecting the complex network of receptors and their transduction machinery. The era of gene targeting and transgenesis in living animals has largely confirmed previous knowledge about the molecular aspects of platelet functions. New insights have also emerged with the perspective of identifying as-yet-unexpected targets for antiplatelet drugs. Blood platelets of transgenic mice have been studied not only to explore hemostasis and thrombosis but also for purposes of general biochemistry and molecular biology. This accounts for the broad range of targeted genes resulting in platelet dysfunction, not all being relevant to pharmacological objectives in terms of antiplatelet drug research. However, these transgenic mice have greatly improved our general understanding of platelet physiology and represent useful models for preclinical pharmacology and basic science.

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  1. INSERM U. 311, Etablissement Français du Sang-Alsace, 10, rue Spielmann, BP N° 36, 67065, Strasbourg Cedex, France

    C. Gachet, B. Hechler, C. Léon, J.-P. Cazenave & F. Lanza

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  1. C. Gachet
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  2. B. Hechler
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  3. C. Léon
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  4. J.-P. Cazenave
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  1. Pharmakologisches Institut, Universität Heidelberg, Im Neuenheimer Feld 366, 69120, Heidelberg, Germany

    Stefan Offermanns

  2. Institut für Pharmakologie und Toxikologie der Universität, Versbacher Straße 9, 97078, Germany

    Lutz Hein

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Gachet, C., Hechler, B., Léon, C., Cazenave, JP., Lanza, F. (2004). Transgenic Animals in Primary Hemostasis and Thrombosis. In: Offermanns, S., Hein, L. (eds) Transgenic Models in Pharmacology. Handbook of Experimental Pharmacology, vol 159. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-18934-0_17

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