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Mice lacking factor VII develop normally but suffer fatal perinatal bleeding

Author

Listed:
  • Elliot D. Rosen

    (Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology
    Center for Transgene Research, University of Notre Dame
    University of Notre Dame)

  • Joyce C. Y. Chan

    (Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology
    Center for Transgene Research, University of Notre Dame
    University of Notre Dame)

  • Esohe Idusogie

    (Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology
    Center for Transgene Research, University of Notre Dame
    University of Notre Dame)

  • Frédéric Clotman

    (Laboratory of Developmental Genetics, University of Louvain)

  • George Vlasuk

    (Corvas International Inc., San Diego)

  • Thomas Luther

    (Institute of Pathology, Technical University of Dresden)

  • Louise R. Jalbert

    (Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology
    Center for Transgene Research, University of Notre Dame
    University of Notre Dame)

  • Sybille Albrecht

    (Institute of Pathology, Technical University of Dresden)

  • Liang Zhong

    (Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology)

  • Ann Lissens

    (Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology)

  • Luc Schoonjans

    (Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology)

  • Lieve Moons

    (Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology)

  • Désiré Collen

    (Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology)

  • Francis J. Castellino

    (Center for Transgene Research, University of Notre Dame
    University of Notre Dame)

  • Peter Carmeliet

    (Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology)

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.

Suggested Citation

  • Elliot D. Rosen & Joyce C. Y. Chan & Esohe Idusogie & Frédéric Clotman & George Vlasuk & Thomas Luther & Louise R. Jalbert & Sybille Albrecht & Liang Zhong & Ann Lissens & Luc Schoonjans & Lieve Moons, 1997. "Mice lacking factor VII develop normally but suffer fatal perinatal bleeding," Nature, Nature, vol. 390(6657), pages 290-294, November.
    • Handle: RePEc:nat:nature:v:390:y:1997:i:6657:d:10.1038_36862
    DOI: 10.1038/36862
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