Mice lacking factor VII develop normally but suffer fatal perinatal bleeding.
Blood coagulation in vivo is initiated by factor VII (FVII) binding to its cellular receptor tissue factor (TF). FVII is the only known ligand for TF, so it was expected that FVII-deficient embryos would have a similar phenotype to TF-deficient embryos, which have defective vitello-embryonic circulation and die around 9.5 days of gestation. Surprisingly, we find that FVII-deficient (FVII-/-) embryos developed normally. FVII-/- mice succumbed perinatally because of fatal haemorrhaging from normal blood vessels. At embryonic day 9.5, maternal-fetal transfer of FVII was undetectable and survival of embryos did not depend on TF-FVII-initiated fibrin formation. Thus, the TF-/- embryonic lethal and the FVII-/- survival-phenotypes suggest a role for TF during embryogenesis beyond fibrin formation.
Rosen
E D
ED
Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Leuven, Belgium.
Chan
J C
JC
Idusogie
E
E
Clotman
F
F
Vlasuk
G
G
Luther
T
T
Jalbert
L R
LR
Albrecht
S
S
Zhong
L
L
Lissens
A
A
Schoonjans
L
L
Moons
L
L
Collen
D
D
Castellino
F J
FJ
Carmeliet
P
P
D000818:Animals; D001777:Blood Coagulation / Q000502:physiology; D046508:Culture Techniques; D005314:Embryonic and Fetal Development; D005167:Factor VII / Q000235:genetics / Q000502:physiology*; D005260:Female; D005313:Fetal Death; D005337:Fibrin / Q000502:physiology; D018390:Gene Targeting; D006470:Hemorrhage / Q000209:etiology* / Q000401:mortality; D006487:Hemostasis / Q000502:physiology; D008431:Maternal-Fetal Exchange; D051379:Mice; D008810:Mice, Inbred C57BL; D016296:Mutagenesis; D011247:Pregnancy; D013925:Thromboplastin / Q000378:metabolism
D005167:Factor VII; D005337:Fibrin; D013925:Thromboplastin