Targeted deletion of murine coagulation factor XII gene-a model for contact phase activation in vivo.
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.
Pauer
Hans-Ulrich
HU
Department of Gynecology and Obstetrics, Medical School, University of Goettingen, Germany.
Renné
Thomas
T
Hemmerlein
Bernhard
B
Legler
Tobias
T
Fritzlar
Saskia
S
Adham
Ibrahim
I
Müller-Esterl
Werner
W
Emons
Guenter
G
Sancken
Ulrich
U
Engel
Wolfgang
W
Burfeind
Peter
P
D000818:Animals; D004789:Enzyme Activation; D005174:Factor XII / Q000235:genetics* / Q000502:physiology*; D005260:Female; D005342:Fibrinolysis; D006487:Hemostasis; D006801:Humans; D040582:Inheritance Patterns; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D010314:Partial Thromboplastin Time; D011247:Pregnancy; D011256:Pregnancy Outcome; D019851:Thrombophilia
D005174:Factor XII