Mice lacking factor VII develop normally but suffer fatal perinatal bleeding

Nature. 1997 Nov 20;390(6657):290-4. doi: 10.1038/36862.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Coagulation / physiology
  • Culture Techniques
  • Embryonic and Fetal Development
  • Factor VII / genetics
  • Factor VII / physiology*
  • Female
  • Fetal Death
  • Fibrin / physiology
  • Gene Targeting
  • Hemorrhage / etiology*
  • Hemorrhage / mortality
  • Hemostasis / physiology
  • Maternal-Fetal Exchange
  • Mice
  • Mice, Inbred C57BL
  • Mutagenesis
  • Pregnancy
  • Thromboplastin / metabolism

Substances

  • Factor VII
  • Fibrin
  • Thromboplastin