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.
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 Name||targeted mutation 1, Denisa D Wagner|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||vWf-; VWF KO|
|Gene Symbol and Name||Vwf, Von Willebrand factor|
|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.|
|Mutations Made By|| |
Cecile Denis, Center for Blood Research
This strain originated on a B6;129S2 background and has been backcrossed to C57BL/6J for at least seven generations before it was made homozygous. When held in a live colony, this strain is maintained by homozygous matings.
When using the vWf KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #003795 in your Materials and Methods section.