Complete antithrombin deficiency in mice results in embryonic lethality
Complete antithrombin deficiency in mice results in embryonic lethality
复制标题
DOI：
10.1172/jci10489
复制
发表时间：
2000-10-01
影响因子：
15.9
通讯作者：
Saito, H
中科院分区：
文献类型：
--
作者：
Ishiguro, K;Kojima, T;Saito, H
抗凝血酶是一种血浆蛋白酶抑制剂，可抑制凝血酶并有助于维持血液流动性。利用靶向基因破坏，我们研究了抗凝血酶在胚胎发生中的作用。抗凝血酶基因（ATIII）破坏杂合子交配小鼠，AIII（+/-），产生预期的孟德尔分布的基因型，直到14.5妊娠日（gd）。然而，15.5 gd时约70%的ATIII（-/-）胚胎和16.5 gd时100%的ATIII（-/-）胚胎死亡，并显示出广泛的皮下出血。对这些胚胎的组织学检查显示，心肌和肝脏中有大量纤维蛋白（原）沉积，但脑或肺中没有。此外，在广泛出血区域未检测到明显的纤维蛋白（原）沉积，表明纤维蛋白原可能由于消耗性凝血病和/或肝功能障碍而降低。这些发现表明，抗凝血酶是胚胎存活所必需的，它在心肌和肝脏的血液凝固调节中起着重要作用。
Antithrombin is a plasma protease inhibitor that inhibits thrombin and contributes to the maintenance of blood fluidity. Using targeted gene disruption, we investigated the role of antithrombin in embryogenesis. Mating mice heterozygous for antithrombin gene (ATIII) disruption, AIII(+/-), yielded the expected Mendelian distribution of genotypes until 14.5 gestational days (gd). However, approximately 70% of the ATIII(-/-) embryos at 15.5 gd and 100% at 16.5 gd had died and showed extensive subcutaneous hemorrhage. Histological examination of those embryos revealed extensive fibrin(ogen) deposition in the myocardium and liver, but not in the brain or lung. Furthermore, no apparent fibrin(ogen) deposition was detected in the extensive hemorrhagic region, suggesting that fibrinogen might be decreased due to consumptive coagulopathy and/or liver dysfunction. These findings suggest that antithrombin is essential for embryonic survival and that it plays an important role in regulation of blood coagulation in the myocardium and liver.