Exons 9 and 10 of these Csk mutant mice are flanked by loxP sites. When crossed with a cre recombinase-expressing strain, these mice are useful for creating tissue-specific knockouts of the gene. They may have applications in studies related to antigen receptor-mediated development and the regulation of T-lineage cell selection.
Alexander Tarakhovsky, The Rockefeller University
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Conditional ready (e.g. floxed), No functional change) | Csk | c-src tyrosine kinase |
Csk (c-src tyrosine kinase) is a negative regulator of Src family protein tyrosine kinases (PTKs). It controls antigen receptor-mediated development and selection of T-lineage cells. Inactivation of the gene in immature thymocytes abrogates the requirement of preTCR, αβTCR and major histocompatibility complex (MHC) class II for the development of CD4+CD8+ double-positive and CD4+ single-positive thymocytes as well as peripheral CD4 αβT-lineage cells. TCR-MHC interactions have no impact on positive selection and commitment to the CD4 lineage in the absence of CSK. However, TCR-mediated negative selection of Csk-deficient, TCR transgenic cells is normal.
Exons 9 and 10 of these Csk mutant mice are flanked by loxP sites. Mice that are homozygous for this conditional allele are viable and fertile.
When crossed with a cre recombinase-expressing strain, these mice are useful for creating tissue-specific knockouts of the gene. Widespread deletion of expression is embryonic lethal.
For example, when bred to mice carrying Tg(Mx1-cre)1Cgn (see Stock No. 003556), interferon-induced Cre-mediated recombination results in disruption of alpha beta T cell development.
A single loxP site was introduced to intron 8 and a herpes simplex virus thymidine kinase (HSV-TK)-Neomycin cassette flanked by loxP sites was inserted into intron 10. The mutation was created in 129P2/OlaHsd-derived E14.1 embryonic stem (ES) cells. The HSVtk-neo cassette was removed by transient transfection of a cre expression vector, leaving exons 9 and 10 flanked by loxP sites. The donating investigator reports that mutant mice were backcrossed to C57BL/6 for more than nine generations (see SNP note below) prior to sending to The Jackson Laboratory. Upon arrival, homozygous sperm was frozen. To generate the live colony, an aliquot of the frozen sperm was used to fertilize oocytes from C57BL/6J inbred females (Stock No. 000664).
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.
Allele Name | targeted mutation 1, Alexander Tarakovsky |
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Allele Type | Targeted (Conditional ready (e.g. floxed), No functional change) |
Allele Synonym(s) | cskfl; cskflox |
Gene Symbol and Name | Csk, c-src tyrosine kinase |
Gene Synonym(s) | |
Strain of Origin | 129P2/OlaHsd |
Chromosome | 9 |
Molecular Note | A loxP site was inserted in intron 8 and a floxed HSVtk-neo selection cassette was inserted in intron 10. The selection cassette was subsequently removed from properly targeted ES cells by transient cre expression leaving exons 9 and 10 flanked by loxP sites. |
Mutations Made By | Alexander Tarakhovsky, The Rockefeller University |
Homozygotes and heterozygotes are viable and fertile.
When using the B6.129P2-Csktm1Tara/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #018320 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous for Csk<tm1Tara> |
Frozen Mouse Embryo | B6.129P2-Csk<tm1Tara>/J | $2595.00 |
Frozen Mouse Embryo | B6.129P2-Csk<tm1Tara>/J | $2595.00 |
Frozen Mouse Embryo | B6.129P2-Csk<tm1Tara>/J | $3373.50 |
Frozen Mouse Embryo | B6.129P2-Csk<tm1Tara>/J | $3373.50 |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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