Fatal haemorrhage and incomplete block to embryogenesis in mice locking coagulation factor V
Fatal haemorrhage and incomplete block to embryogenesis in mice locking coagulation factor V
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DOI：
10.1038/384066a0
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发表时间：
1996-11-07
期刊：
影响因子：
64.8
通讯作者：
Ginsburg, D
中科院分区：
文献类型：
--
作者：
Cui, JS;OShea, KS;Ginsburg, D
凝血因子V是凝血酶原活化为凝血酶的关键辅因子，是纤维蛋白血凝块生成的倒数第二步（1，2）。因子V的遗传缺陷导致先天性出血性疾病（副血友病）（3），而使因子V对失活具有抗性的突变的遗传是血栓形成的重要风险因素（4，5）。我们在这里报告，大约一半的纯合子胚胎缺乏因子V（F upper（-/-）），这已经产生的基因靶向，死亡在胚胎（E）天9-10，可能是由于在卵黄囊脉管系统的异常。剩余的F upper（-/-）小鼠正常进展至足月，但在2小时内或出生时死于大出血。与通常与其他凝血因子缺乏相关的较温和表型一起考虑（6，7），我们的研究结果证明了常见凝血途径的主要作用和凝血酶原酶活性对功能因子V的绝对要求。他们还提供了直接的证据，除了纤维蛋白凝块的形成，凝血酶的其他关键止血功能的存在，并确定了以前未被认识到的作用，凝血系统在早期哺乳动物的发展。
COAGULATION factor V is a critical cofactor for the activation of prothrombin to thrombin, the penultimate step in the generation of a fibrin blood clot(1,2). Genetic deficiency of factor V results in a congenital bleeding disorder (parahaemophilia)(3), whereas inheritance of a mutation rendering factor V resistant to inactivation is an important risk factor for thrombosis(4,5). We report here that approximately half of homozygous embryos deficient in factor V (F upsilon(-/-)), which have been generated by gene targeting, die at embryonic day (E) 9-10, possibly as a result of an abnormality in the yolk-sac vasculature. The remaining F upsilon(-/-) mice progress normally to term, but die from massive haemorrhage within 2 hours or birth. Considered together with the milder phenotypes generally associated with deficiencies of other clotting factors(6,7), our findings demonstrate the primary role of the common coagulation pathway and the absolute requirement for functional factor V for prothrombinase activity. They also provide direct evidence for the existence of other critical haemostatic functions for thrombin in addition to fibrin clot formation, and identify a previously unrecognized role for the coagulation system in early mammalian development.