Ishiguro K, Kojima T, Kadomatsu K, Nakayama Y, Takagi A, Suzuki M, Takeda N, Ito M, Yamamoto K, Matsushita T, Kusugami K, Muramatsu T, Saito H
First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan.
J Clin Invest. 2000 Oct;106(7):873-8. doi: 10.1172/JCI10489.
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, ATIII(+/-), 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.
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。我们利用靶向基因敲除技术研究了抗凝血酶在胚胎发育中的作用。将抗凝血酶基因（ATIII）敲除的杂合子小鼠（ATIII(+/-)）进行交配，在妊娠14.5天（gd）之前，基因型的分布符合预期的孟德尔遗传规律。然而，在15.5 gd时，约70%的ATIII(-/-)胚胎死亡，在16.5 gd时，100%的胚胎死亡，并出现广泛的皮下出血。对这些胚胎进行组织学检查发现，心肌和肝脏中有广泛的纤维蛋白（原）沉积，但脑和肺中没有。此外，在广泛的出血区域未检测到明显的纤维蛋白（原）沉积，这表明纤维蛋白原可能因消耗性凝血病和/或肝功能障碍而减少。这些发现表明，抗凝血酶对胚胎存活至关重要，并且在心肌和肝脏的血液凝固调节中起重要作用。
