A Mouse Model of Severe Von Willebrand Disease: Defects in Hemostasis and Thrombosis

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 d...

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Bibliographic Details
Published in:	Proceedings of the National Academy of Sciences - PNAS 1998-08, Vol.95 (16), p.9524-9529
Main Authors:	Denis, Cecile, Methia, Nassia, Frenette, Paul S., Rayburn, Helen, Ullman-Cullere, Mollie, Hynes, Richard O., Wagner, Denisa D.
Format:	Article
Language:	eng
Subjects:	Animals Antibodies Arterioles Biological Sciences Bleeding Blood Blood plasma Blood vessels Disease Disease Models, Animal Exons Female Genes Hemostasis - genetics Medical research Mice Mice, Inbred C57BL Mice, Mutant Strains Phenotype Platelets Rodents Thrombosis Thrombosis - genetics von Willebrand Diseases - genetics von Willebrand Diseases - physiopathology von Willebrand Factor - genetics
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Summary:	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 von Willebrand disease and will be very useful for investigating the role of vWf in normal physiology and in disease models.
ISSN:	0027-8424 1091-6490