Abstract
Blood coagulation in vivo is initiated by factor VII (FVII) binding to its cellular receptor tissue factor (TF)1,2,3,4. 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 gestation5,6,7,8. 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.
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Acknowledgements
We thank U. Hedner and M. Ezban (Novo Nordisk, Gentofte, Denmark) for the gift of rFVIIa, P. Bergum (Corvas, San Diego, CA) for rNAPc2 measurements, J. W. Fenton (Albany, NY) for thrombin, T. Edgington and E. Conway for discussions and M. Dewerchin, V. Attenburrow, A. Bouché, I. Cornelissen, S. Danloy, F. Decock, M. Deprez, M. DeWit, E. Gils, L. Kieckens, A. Manderveld, A. Vandenhoeck, A. Van den Boomen and S. Wyns (CTG); J. Picard and N. Pacico (LDG) and H. Fehrenbach (IP) for help. These studies were supported by a grant from the National Institutes of Health and the Kleiderer/Pezold Family endowed professorship (to F.J.C.). J.C.Y.C. is a recipient of the Raymond Tower Endowed Graduate Fellowship.
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Rosen, E., Chan, J., Idusogie, E. et al. Mice lacking factor VII develop normally but suffer fatal perinatal bleeding. Nature 390, 290–294 (1997). https://doi.org/10.1038/36862
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DOI: https://doi.org/10.1038/36862
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