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)(1-4). FVII is the only known ligand for TF, so it was expected that FVII-deficient embryos would h ave a similar phenotype to TF-deficient embryos, which have defective vitello-embryonic circulation and die around 9.5 days of gestation(5-8 ), Surprisingly, we find that FVII-deficient (FVII-/-) embryos develop ed normally, FVII-/- mice succumbed perinatally because of fatal haemo rrhaging from normal blood vessels. At embryonic day 9.5, maternal-fet al transfer of FVII was undetectable and survival of embryos did not d epend on TF-FVII-initiated fibrin formation. Thus, the TF-/- embryonic lethal and the FVII-/- survival-phenotypes suggest a role for TF duri ng embryogenesis beyond fibrin formation.