PLASMINOGEN DEFICIENCY CAUSES SEVERE THROMBOSIS BUT IS COMPATIBLE WITH DEVELOPMENT AND REPRODUCTION
PLASMINOGEN DEFICIENCY CAUSES SEVERE THROMBOSIS BUT IS COMPATIBLE WITH DEVELOPMENT AND REPRODUCTION
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DOI：
10.1101/gad.9.7.794
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发表时间：
1995-04-01
影响因子：
10.5
通讯作者：
DEGEN, JL
中科院分区：
文献类型：
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作者：
BUGGE, TH;FLICK, MJ;DEGEN, JL
产生纤溶酶原（Plg）缺陷小鼠是为了定义这种关键纤溶蛋白及其蛋白水解衍生物纤溶酶和血管抑制素在发育、止血和生殖中的生理作用。Plg（-/-）小鼠完成胚胎发育，存活至成年，并且具有生育能力。根据突变型Plg等位基因的孟德尔传递模式，没有证据表明Plg（-/-）螨的胎儿丢失。此外，胚胎发育在缺乏内源性、同胞来源或母体Plg的情况下继续足月。然而，Plg（-/-）小鼠易患严重血栓形成，并且年幼的动物在肝、胃、结肠、直肠、肺、胰腺和其他组织中出现多个自发性血栓性病变。在5- 21周龄的小鼠中，肝脏中的纤维素沉积是一致的发现，胃肠道和直肠组织中的溃疡病变是常见的。考虑到纤溶酶和纤溶酶原激活物的蛋白水解激活之间的良好联系，一个显著的发现是Plg（-/-）小鼠尿液中活性尿激酶型纤溶酶原激活物的水平不受影响。因此，Plg在纤维蛋白溶解和止血中起关键作用，但对于尿激酶酶原活化、发育或生长至性成熟不是必需的。
Plasminogen (Plg)-deficient mice were generated to define the physiological roles of this key fibrinolytic protein and its proteolytic derivatives, plasmin and angiostatin, in development, hemostasis, and reproduction. Plg(-/-) mice complete embryonic development, survive to adulthood, and are fertile. There is no evidence of fetal loss of Plg(-/-) mite based on the Mendelian pattern of transmission of the mutant Plg allele.Furthermore, embryonic development continues to term in the absence of endogenous, sibling-derived, or maternal Plg. However, Plg(-/-) mice are predisposed to severe thrombosis, and young animals developed multiple spontaneous thrombotic lesions in liver, stomach, colon, rectum, lung, pancreas, and other tissues. Fibrin deposition in the liver was a uniform finding in 5- to 21-week-old mice, and ulcerated lesions in the gastrointestinal tract and rectal tissue were common. A remarkable finding, considering the well-established linkage between plasmin and the proteolytic activation of plasminogen activators, was that the level of active urokinase-type plasminogen activator in urine was unaffected in Plg(-/-) mice. Therefore, Plg plays a pivotal role in fibrinolysis and hemostasis but is not essential for urokinase proenzyme activation, development, or growth to sexual maturity.