Mouse models of thrombosis: thrombomodulin

Hartmut Weiler

doi:10.1160/TH04-05-0307

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 92(03): 467-477
DOI: 10.1160/TH04-05-0307

Theme Issue Article

Schattauer GmbH

Mouse models of thrombosis: thrombomodulin

Hartmut Weiler

¹Blood Research Institute, Blood Center of Southeastern Wisconsin, Medical College of Wisconsin, Department of Physiology, Milwaukee, Wisconsin, USA

› Author Affiliations

Abstract

Summary

This review describes animal models of TM-deficiency that cause thrombosis in mice. Thrombomodulin (TM) is a key component of the protein C anticoagulant pathway by facilitating the activation of protein C by thrombin. In addition, TM integrates fibrinolytic and anti-inflammatory responses in a manner that is in part independent of protein C and thrombin. A series of genetically modified mouse strains is available in which the various and distinct functions of TM have been altered by means of site-directed mutagenesis of the TM gene locus (Thbd). The focus of the current review is the pathological activation of the hemostatic mechanism in mice with altered TM function (the pathologic activation of the hemostatic mechanism). The analysis of these mouse models has revealed novel and in part organ-specific functions of TM, most notably in the vascular bed of the placenta. In these mouse models, the severity and phenotypic expression of thrombosis is highly variable and is dependent on interaction with secondary genetic or environmental modifiers. The mutant mouse strains replicate important aspects of thrombophilia and thrombosis in humans, and provide a valuable resource to validate existing, and develop novel concepts of disease mechanisms in human patients.

Keywords

Thrombomodulin - protein C - mouse models

Full Text

References

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