Vav1 (vav 1 oncogene) knockout mice exhibit deficient T cell development and proliferation, as well as impaired B cell proliferation, NK cell function and +/- selection of class I and II restricted thymocytes.
Victor L.J. Tybulewicz, MRC National Institute for Medical Research
VAV1 (vav 1 oncogene) is a guanine nucleotide exchange factor for Rho family GTPases. It is expressed in all hematopoietic cells, including B and T lymphocytes. VAV1 is tyrosine phosphorylated following BCR or TCR stimulation and this phosphorylation regulates its exchange activity. In this strain, a neomycin cassette was used to disrupt exon 8, which codes for part of the DH (Dbl homology) domain of the protein. No detectable VAV1 protein is made. Mice homozygous for the mutation are viable and fertile. Vav1-deficient mice exhibit impaired T cell development, with a partial block at the pre-TCR checkpoint between double negative and double positive (DP) thymocytes, and defects in positive and negative selection of class I- and II-restricted thymocytes. DP thymocytes are reduced two-fold, CD4+ and CD8+ single positive T cells are reduced 7 to 8 fold.
Vav1-deficient T cells are impaired in TCR-induced proliferation, IL2 secretion, calcium flux, activation of Akt and ERK MAP kinases, and LFA1-dependent adhesion. Vav11-deficient T cells are defective in the formation of antigen-specific conjugates with antigen presenting cells and in cell polarization. Vav1-deficient B cells are defective in BCR-induced proliferation and calcium flux, and in LPS-induced proliferation. Vav1-deficient mice mount defective T-dependent antibody responses. Vav1-deficient NK cells develop normally but show reduced ability to lyse tumor cells
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
The targeting vector was designed to disrupt exon 8 (ENSMUSE00000138978) of the Vav1 gene coding for part of the DH (Dbl homology) domain of the protein, by inserting the neomycin resistance gene at a SmaI site. The construct was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were bred to 129S8/SvEvNimr mice and then to C57BL/6JNimr mice for 10 generations. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.
|Allele Name||targeted mutation 1, Victor L J Tybulewicz|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Vav-; Vav1-|
|Gene Symbol and Name||Vav1, vav 1 oncogene|
|Strain of Origin||129S2/SvPas|
|Molecular Note||The gene was disrupted by insertion of a PGK-neo cassette into a coding exon at nucleotide 793. No full-length or partial protein product was detectable in thymocytes and splenic B and T cells from homozygous mutant animals via Western blot analysis.|
|Mutations Made By|| |
Victor Tybulewicz, MRC National Institute for Medical Research
While maintaining a live colony, these mice are bred as homozygotes.
When using the B6.129S-Vav1tm1Tyb/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #019379 in your Materials and Methods section.
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