Rosen E D, Chan J C, Idusogie E, Clotman F, Vlasuk G, Luther T, Jalbert L R, Albrecht S, Zhong L, Lissens A, Schoonjans L, Moons L, Collen D, Castellino F J, Carmeliet P
Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Leuven, Belgium.
Nature. 1997 Nov 20;390(6657):290-4. doi: 10.1038/36862.
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.
体内血液凝固由因子VII（FVII）与其细胞受体组织因子（TF）结合启动。FVII是TF唯一已知的配体，因此预计FVII缺陷胚胎会具有与TF缺陷胚胎相似的表型，后者存在卵黄囊 - 胚胎循环缺陷并在妊娠约9.5天时死亡。令人惊讶的是，我们发现FVII缺陷（FVII-/-）胚胎发育正常。FVII-/-小鼠在围产期死亡，原因是正常血管发生致命性出血。在胚胎第9.5天，未检测到FVII的母胎转移，胚胎存活不依赖于TF-FVII启动的纤维蛋白形成。因此，TF-/-胚胎致死和FVII-/-存活表型表明TF在胚胎发生过程中的作用超出了纤维蛋白形成。
