Separation of VWF domain function using gene-targeted mic

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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.