Fatal embryonic bleeding events in mice lacking tissue factor, the cell-associated initiator of blood coagulation
Fatal embryonic bleeding events in mice lacking tissue factor, the cell-associated initiator of blood coagulation
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DOI：
10.1073/pnas.93.13.6258
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发表时间：
1996-06-25
影响因子：
11.1
通讯作者：
Degen, JL
中科院分区：
文献类型：
--
作者：
Bugge, TH;Xiao, Q;Degen, JL
组织因子（TF）是凝血因子VII/VIIa的细胞受体，是一种膜结合糖蛋白，通常被认为是血液凝固的主要生理发起者。为了更详细地定义TF在发育和止血中的生理作用，在小鼠中破坏了TF基因，失活的TF等位基因杂合的小鼠表达了大约一半的TF活性野生型小鼠，但表型正常。纯合子TF-/-仔鼠从未在杂合子小鼠杂交中出生，中期妊娠胚胎分析显示，TF-/-胚胎在子宫内8.5 ~ 10.5天死亡。第9.5天时，TF-/-胚胎与TF+/+和TF+/-胎仔形态不同，发育迟缓，水肿，组织学研究表明，早期器官发生正常，TF-/-胚胎的初始衰竭表现为出血，导致胚胎外和胚胎血管中的胚胎红细胞渗漏。这些研究表明，在胚胎和胚胎外血管融合和血液循环开始时，TF在胚胎发育中建立和/或维持血管完整性方面起着不可或缺的作用。
Tissue factor (TF) is the cellular receptor for coagulation factor VII/VIIa and is the membrane-bound glycoprotein that is generally viewed as the primary physiological initiator of blood coagulation, To define in greater detail the physiological role of TF in development and hemostasis, the TF gene was disrupted in mice, Mice heterozygous for the inactivated TF allele expressed approximately half the TF activity of wild-type mice but were phenotypically normal, However, homozygous TF-/- pups were never born in crosses between heterozygous mice, Analysis of mid-gestation embryos showed that TF-/- embryos die in utero between days 8.5 and 10.5. TF-/- embryos were morphologically distinct from their TF+/+ and TF+/- littermates after day 9.5 in that they were Dale, edematous, and growth retarded, Histological studies showed that early organogenesis was normal, The initial failure in TF-/- embryos appeared to be hemorrhaging, leading to the leakage of embryonic red cells from both extraembryonic and embryonic vessels, These studies indicate that TF plays an indispensable role in establishing and/or maintaining vascular integrity in the developing embryo at a time when embryonic and extraembryonic vasculatures are fusing and blood circulation begins.