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)||Vav1tm1Tyb; targeted mutation 1, Victor L J Tybulewicz|
|Gene Symbol and Name||Vav1, vav 1 oncogene|
|Gene Synonym(s)||VAV; Vav|
|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.
|Heterozygous for Vav1<tm1Tyb>|
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.
MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.
Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.
In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.
MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.
Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.