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Mice lacking factor VII develop normally but suffer fatal perinatal bleeding

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Rosen, ED Chan, JCY Idusogie, E Clotman, Frédéric [UCL] Vlasuk, G Carmeliet, P

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 have 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 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.

Document type Article de périodique (Journal article) – Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.
Publication date 1997
Language Anglais
Journal information "Nature : international weekly journal of science" - Vol. 390, no. 6657, p. 290-4 (1997)
Peer reviewed yes
Publisher Macmillan Magazines Ltd (London)
issn 0028-0836
Publication status Publié
Affiliation UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire
MESH Subject Thromboplastin - metabolism ; Pregnancy ; Mutagenesis ; Mice, Inbred C57BL ; Mice ; Maternal-Fetal Exchange ; Hemostasis - physiology ; Hemorrhage - etiology - mortality ; Gene Targeting ; Fibrin - physiology ; Fetal Death ; Female ; Factor VII - genetics - physiology ; Embryonic and Fetal Development ; Culture Techniques ; Blood Coagulation - physiology ; Animals
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Bibliographic reference Rosen, ED ; Chan, JCY ; Idusogie, E ; Clotman, Frédéric ; Vlasuk, G ; et. al. Mice lacking factor VII develop normally but suffer fatal perinatal bleeding. In: Nature : international weekly journal of science, Vol. 390, no. 6657, p. 290-4 (1997)
Permanent URL http://hdl.handle.net/2078.1/45862