Xue J, Wu Q, Westfield L A, Tuley E A, Lu D, Zhang Q, Shim K, Zheng X, Sadler J E
Department of Medicine, Department of Biochemistry and Molecular Biophysics, Barnes-Jewish Hospital and Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110, USA.
Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7603-7. doi: 10.1073/pnas.95.13.7603.
Deficiency of blood coagulation factor V or tissue factor causes the death of mouse embryos by 10.5 days of gestation, suggesting that part of the blood coagulation system is necessary for development. This function is proposed to require either generation of the serine protease thrombin and cell signaling through protease-activated receptors or an activity of tissue factor that is distinct from blood clotting. We find that murine deficiency of prothrombin clotting factor 2 (Cf2) was associated with the death of approximately 50% of Cf2(-/-) embryos by embryonic day 10.5 (E10.5), and surviving embryos had characteristic defects in yolk sac vasculature. Most of the remaining Cf2(-/-) embryos died by E15.5, but those surviving to E18.5 appeared normal. The rare Cf2(-/-) neonates died of hemorrhage on the first postnatal day. These studies suggest that a part of the blood coagulation system is adapted to perform a developmental function. Other mouse models show that the absence of platelets or of fibrinogen does not cause fetal wastage. Therefore, the role of thrombin in development may be independent of its effects on blood coagulation and instead may involve signal transduction on cells other than platelets.
凝血因子V或组织因子的缺乏会导致小鼠胚胎在妊娠10.5天时死亡，这表明部分凝血系统对胚胎发育是必需的。有人提出，这一功能需要通过蛋白酶激活受体产生丝氨酸蛋白酶凝血酶并进行细胞信号传导，或者需要组织因子具有不同于血液凝固的活性。我们发现，小鼠凝血酶原凝血因子2（Cf2）缺乏与约50%的Cf2（-/-）胚胎在胚胎第10.5天（E10.5）死亡有关，存活的胚胎在卵黄囊血管系统中存在特征性缺陷。其余大多数Cf2（-/-）胚胎在E15.5时死亡，但存活至E18.5的胚胎看起来正常。罕见的Cf2（-/-）新生小鼠在出生后第一天死于出血。这些研究表明，部分凝血系统适用于执行发育功能。其他小鼠模型显示，缺乏血小板或纤维蛋白原不会导致胎儿流失。因此，凝血酶在发育中的作用可能与其对血液凝固作用无关，而可能涉及除血小板外其他细胞上的信号转导。
