A mouse model of severe von Willebrand disease: Defects in hemostasis and thrombosis

Cécile Denis, Nassia Methia, Paul S. Frenette, Helen Rayburn, Mollie Ullman-Culleré, Richard O. Hynes, Denisa D. Wagner

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440 Scopus citations


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 ≃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 yon Willebrand disease and will be very useful for investigating the role of vWf in normal physiology and in disease models.

Original languageEnglish (US)
Pages (from-to)9524-9529
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number16
StatePublished - Aug 4 1998
Externally publishedYes

ASJC Scopus subject areas

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