Incomplete embryonic lethality and fatal neonatal hemorrhage caused by prothrombin deficiency in mice.
Incomplete embryonic lethality and fatal neonatal hemorrhage caused by prothrombin deficiency in mice.
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小鼠凝血酶原缺乏引起的不完全胚胎致死和致命性新生儿出血。
DOI：
10.1073/pnas.95.13.7603
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发表时间：
1998
影响因子：
11.1
通讯作者：
Sadler,JE
中科院分区：
文献类型：
--
作者：
Xue,J;Wu,Q;Westfield,LA;Tuley,EA;Lu,D;Zhang,Q;Shim,K;Zheng,X;Sadler,JE
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于发育是必需的。该功能被认为需要丝氨酸蛋白酶凝血酶的产生和通过蛋白酶激活受体的细胞信号传导或不同于血液凝固的组织因子的活性。我们发现，小鼠凝血酶原凝血因子 2 (Cf2) 缺乏与胚胎第 10.5 天 (E10.5) 时大约 50% 的 Cf2−/− 胚胎死亡有关，并且存活的胚胎在卵黄囊脉管系统中具有特征性缺陷。大多数剩余的 Cf2−/− 胚胎在 E15.5 时死亡，但那些存活到 E18.5 的胚胎似乎正常。罕见的 Cf2−/− 新生儿在出生后第一天就因出血死亡。这些研究表明，凝血系统的一部分适合执行发育功能。其他小鼠模型表明，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的作用无关，而是可能涉及除血小板以外的细胞上的信号转导。
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.