A mouse model of severe von Willebrand disease:: Defects in hemostasis and thrombosis
A mouse model of severe von Willebrand disease:: Defects in hemostasis and thrombosis
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DOI：
10.1073/pnas.95.16.9524
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发表时间：
1998-08-04
影响因子：
11.1
通讯作者：
Wagner, DD
中科院分区：
文献类型：
--
作者：
Denis, C;Methia, N;Wagner, DD
冯·维勒布兰德因子 (vWf) 缺乏会导致人类严重的冯·维勒布兰德病。我们通过基因靶向建立了这种疾病的小鼠模型。 vWf 缺陷小鼠出生时表现正常；他们是有生存能力和生育能力的。在纯合突变小鼠的血浆、血小板或内皮细胞中均未检测到 vWf 和 vWf 前多肽（冯维勒布兰德抗原 II）。突变小鼠表现出止血缺陷，出血时间高度延长，大约 10% 的新生儿出现自发性出血事件。与人类疾病一样，由于缺乏 vWf 提供的保护，这些小鼠的 VIII 因子水平大幅降低。在血管损伤的体内模型中，突变小鼠的缺陷性血栓形成也很明显。在该模型中，外置的肠系膜灌注了氯化铁，并通过活体显微镜观察到荧光标记的血小板的积累。我们得出的结论是，这些小鼠非常接近严重的人类血管性血友病，对于研究 vWf 在正常生理学和疾病模型中的作用非常有用。
von Willebrand factor (vWf) deficiency causes severe von Willebrand disease in humans. We generated a mouse model for this disease by using gene targeting. vWf-deficient mice appeared normal at birth; they were viable and fertile. Neither vWf nor vWf propolypeptide (von Willebrand antigen II) were detectable in plasma, platelets, or endothelial cells of the homozygous mutant mice. The mutant mice exhibited defects in hemostasis with a highly prolonged bleeding time and spontaneous bleeding events in approximate to 10% of neonates, As in the human disease, the factor VIII level in these mice was reduced strongly as a result of the lack of protection provided by vWf. Defective thrombosis in mutant mice was also evident in an in vivo model of vascular injury, In this model, the exteriorized mesentery was superfused with ferric chloride and the accumulation of fluorescently labeled platelets was observed by intravital microscopy, We conclude that these mice very closely mimic severe human von Willebrand disease and will be very useful for investigating the role of vWf in normal physiology and in disease models.