Characterization of Mouse Thrombin-activatable Fibrinolysis Inhibitor

Pauline F. Marx; Gerry T. M. Wagenaar; Arie Reijerkerk; Margriet J. Tiekstra; Agnes G. S. H. van Rossum; Martijn F. B. G. Gebbink; Joost C. M. Meijers

doi:10.1055/s-0037-1613802

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2000; 83(02): 297-303
DOI: 10.1055/s-0037-1613802

Rapid Communication

Schattauer GmbH

Characterization of Mouse Thrombin-activatable Fibrinolysis Inhibitor

Autoren

Pauline F. Marx

¹From the Thrombosis and Haemostasis Laboratory, Department of Haematology, University Medical Center, Utrecht

²Institute for Biomembranes, University of Utrecht, The Netherlands
Gerry T. M. Wagenaar

¹From the Thrombosis and Haemostasis Laboratory, Department of Haematology, University Medical Center, Utrecht

²Institute for Biomembranes, University of Utrecht, The Netherlands
Arie Reijerkerk

³Department of Medical Oncology, University Medical Center, Utrecht, The Netherlands
Margriet J. Tiekstra

¹From the Thrombosis and Haemostasis Laboratory, Department of Haematology, University Medical Center, Utrecht

²Institute for Biomembranes, University of Utrecht, The Netherlands
Agnes G. S. H. van Rossum

¹From the Thrombosis and Haemostasis Laboratory, Department of Haematology, University Medical Center, Utrecht

²Institute for Biomembranes, University of Utrecht, The Netherlands
Martijn F. B. G. Gebbink

³Department of Medical Oncology, University Medical Center, Utrecht, The Netherlands
Joost C. M. Meijers

¹From the Thrombosis and Haemostasis Laboratory, Department of Haematology, University Medical Center, Utrecht

²Institute for Biomembranes, University of Utrecht, The Netherlands

Abstract

Summary

Based on in vitro studies, thrombin-activatable fibrinolysis inhibitor (TAFI) has been hypothesized as a link between coagulation and fibrinolysis, but the physiological role of TAFI in vivo has not yet been established. To anticipate on the availability of genetically modified mouse models, we studied the endogenous expression of TAFI in mice. Functional TAFI was found in mouse plasma. TAFI mRNA was only detectable in the liver, showing a hepatocyte-specific expression with a pericentral lobular distribution pattern. The murine TAFI cDNA was cloned and sequenced. The deduced amino acid sequence revealed that murine TAFI is highly identical to human TAFI. The murine cDNA was stably expressed and the activated recombinant protein was functionally active; it converted the substrate hippuryl-arginine, and prolonged the clot lysis time of TAFI depleted plasma. We conclude that mice have functional TAFI in plasma, which is highly similar to human TAFI. Therefore, genetically modified mice may provide useful models to study the role of TAFI in vivo.

Abbreviations: TAFI, thrombin-activatable fibrinolysis inhibitor; CPI, carboxypeptidase inhibitor from potato tubers; CPN, carboxypeptidase N; t-PA, tissue-type plasminogen activator; PPACK, H-D-Phe-Pro-Arg-chloromethylketone.

Keywords

Coagulation - fibrinolysis - thrombin-activatable fibrinolysis inhibitor

Volltext

Referenzen

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