Targeted deletion of murine coagulation factor XII gene-a model for contact phase activation in vivo

Hans-Ulrich Pauer; Thomas Renné; Bernhard Hemmerlein; Tobias Legler; Saskia Fritzlar; Ibrahim Adham; Werner Müller-Esterl; Guenter Emons; Ulrich Sancken; Wolfgang Engel; Peter Burfeind

doi:10.1160/TH04-04-0250

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 92(03): 503-508
DOI: 10.1160/TH04-04-0250

Theme Issue Article

Schattauer GmbH

Targeted deletion of murine coagulation factor XII gene-a model for contact phase activation in vivo

Authors

Hans-Ulrich Pauer

¹Department of Gynecology and Obstetrics, Medical School, University of Goettingen, Germany
Thomas Renné

²Junior Group at the Institute of Clinical Biochemistry and Pathobiochemistry, University of Wuerzburg, Germany
Bernhard Hemmerlein

³Department of Pathology, Medical School, University of Goettingen, Germany
Tobias Legler

⁴Department of Transfusion Medicine, Medical School, University of Goettingen, Germany
Saskia Fritzlar

⁵Institute of Human Genetics, University of Goettingen, Germany
Ibrahim Adham

⁵Institute of Human Genetics, University of Goettingen, Germany
Werner Müller-Esterl

⁶Institute of Biochemistry II, Medical School, University of Frankfurt, Germany
Guenter Emons

¹Department of Gynecology and Obstetrics, Medical School, University of Goettingen, Germany
Ulrich Sancken

⁵Institute of Human Genetics, University of Goettingen, Germany
Wolfgang Engel

⁵Institute of Human Genetics, University of Goettingen, Germany
Peter Burfeind

⁵Institute of Human Genetics, University of Goettingen, Germany

Abstract

Summary

To analyze the biological role of factor XII (FXII, Hageman Factor) in vivo, we generated mice deficient for FXII using a gene targeting approach on two distinct genetic backgrounds, i.e. mixed C57Bl/6J X 129X1/SvJ and inbred 129X1/SvJ. Homozygous FXII knockout (FXII-/-) mice showed no FXII plasma activity and had a markedly prolonged activated partial thromboplastin time (aPTT). In contrast, coagulation factors XI, VIII, IX, X,VII,V, II and fibrinogen did not differ between FXII-/- mice and their wild-type littermates. Heterozygous matings segregated according to the Mendelian inheritance indicating that FXII deficiency does not increase fetal loss. Furthermore, matings of FXII-/- males and FXII-/females resulted in normal litter sizes demonstrating that total FXII deficiency in FXII-/females does not affect pregnancy outcome. Also, gross and histological anatomy of FXII-/mice was indistinguishable from that of their wild-type littermates on both genetic backgrounds. Thus it appears that deficiency of murine FXII does not cause thrombophilia or impaired fibrinolysis in vivo. These results indicate that FXII deficiency does not affect hemostasis in vivo and we anticipate that the FXII-/mice will be helpful to elucidate the biological role(s) of FXII in health and disease.

Keywords

Coagulation - factor XII - gene targeting

Full Text

References

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