Separation of VWF domain function using gene-targeted mic

血管性血友病因子是一种多功能止血因子，在早期止血中起重要作用。VWF的多功能是通过其多域结构来实现的，每个功能模块可以贡献不同的止血功能。我们将VWFK1362A型敲击小鼠与其中一个重要的GPIB结合位点Lys1362突变为ALA和VWF-/-小鼠，建立了功能性/非功能性VWF模型的体内数量变异模型。我们还引入了CAST/EI背景，以提高基础血浆VWF水平。VWFK1362A表现出严重的出血性质，提示VWF GPIB结合是维持止血的关键功能。然而，由于不育和捕食，VWFK1362A和VWF-/-小鼠之间的杂交部分成功。进一步的研究将揭示VWF在哺乳动物中维持止血的定量功能。

von Willebrand factor is a multi-functional hemostatic factor that plays an important role of primary hemostasis. The VWF multi-function is accomplished by its multi-domain structure and each functional module may contribute to different hemostatic functions. We crossed VWFK1362A knock in mouse of which Lys1362, an important GPIb binding site, is mutated to Ala and VWF-/- mouse to yield the in vivo model of quantitative variations of functional/nonfunctional VWF models. We also introduced CAST/Ei background to increase the basic plasma VWF levels. VWFK1362A showed severe bleeding diathesis, suggesting VWF GPIb binding is pivotal function to maintain hemostasis. Crossing between VWFK1362A and VWF-/- mouse, however, was partially successful, because of infertility and prey. Further investigation would reveal quantitative function of VWF to maintain hemostasis in mammals.