Targeted deletion of murine coagulation factor XII gene-a model for contact phase activation in vivo
Hans-Ulrich Pauer
1
Department of Gynecology and Obstetrics, Medical School, University of Goettingen, Germany
,
Thomas Renné
2
Junior Group at the Institute of Clinical Biochemistry and Pathobiochemistry, University of Wuerzburg, Germany
,
Bernhard Hemmerlein
3
Department of Pathology, Medical School, University of Goettingen, Germany
,
Tobias Legler
4
Department of Transfusion Medicine, Medical School, University of Goettingen, Germany
,
Saskia Fritzlar
5
Institute of Human Genetics, University of Goettingen, Germany
,
Ibrahim Adham
5
Institute of Human Genetics, University of Goettingen, Germany
,
Werner Müller-Esterl
6
Institute of Biochemistry II, Medical School, University of Frankfurt, Germany
,
Guenter Emons
1
Department of Gynecology and Obstetrics, Medical School, University of Goettingen, Germany
,
Ulrich Sancken
5
Institute of Human Genetics, University of Goettingen, Germany
,
Wolfgang Engel
5
Institute of Human Genetics, University of Goettingen, Germany
,
Peter Burfeind
5
Institute of Human Genetics, University of Goettingen, Germany
› Author AffiliationsFinancial support: This work was supported by grants from the Forschungsfoerderungsprogramm of the Medical Faculty, University of Goettingen, Germany (H.-U. P.) and the Deutsche Forschungsgemeinschaft (SFB355 to T.R.), Germany.
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
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