B6.129S2-Vwf^tm1Wgr/J

Stock number: 003795
Product name: vWf KO
Research areas: Hematological Research

Description

These Vwf knock-out mice exhibit defects in hemostasis characterized by prolonged bleeding times.

Detailed description

Mice that are homozygous null for the Vwf gene are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No Vwf protein product is detected in platelets, plasma, heart or lung endothelium. Null mice exhibit defects in hemostasis characterized by prolonged bleeding times in all mice with spontaneous bleeding events observed in ten percent of neonates. Intravital microscopic analysis indicates a complete absence of thrombus formation following vascular injury. Observed levels of factor VIII are reduced to twenty percent of that seen in wild type mice. Although heterozygous mice carrying a single null allele exhibit no defects in hemostasis, they do have reduced levels of factor VIII (57 percent that of wildtype) making them a suitable model for type 1 von Willebrand disease. Characteristics displayed by homozygous null animals qualify them as an appropriate model for severe (type 3) von Willebrand disease.

Development

A targeting vector containing a neomycin resistance gene driven by a mouse phosphoglycerate kinase promoter flanked by two herpes simplex virus thymidine kinase cassettes was used to disrupt exons four and five of the Vwf gene. The construct was introduced into 129S2/SvPas-derived D3 embryonic stem (ES) cells by electroporation. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric male animals were backcrossed to C57BL/6J females.

Allele

Symbol: Vwf^tm1Wgr
Name: targeted mutation 1, Denisa D Wagner
MGI accession ID: MGI:2153009
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: vWf-; VWF KO
Marker symbol: Vwf
Marker name: Von Willebrand factor
Marker synonyms: 6820430P06Rik; B130011O06Rik; F8VWF; VWD
Chromosome: 6
Strain of origin: 129S2/SvPas
Molecular note: A neomycin cassette was inserted into intron 5. Northern blot analysis revealed that no normal transcripts were present in homozygous mice, and immunofluorescence experiments demonstrated that the protein was not present in blood smears of homozygous mice.