Itk-/- mice may be useful for studying the role of ITK in the proliferation and activation of lymphocytes.
Pamela L Schwartzberg, National Human Genome Research Institute, National Institutes of Health (NHGRI, NIH)
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Itk | IL2 inducible T cell kinase |
Itk-/- mice have a STOP codon inserted into exon 2, and a neo cassette replaces exon 4 and part of exon 3, of the IL2 inducible T cell kinase (Itk) gene, abolishing gene expression. Itk is a member of Tec family of tyrosine kinases. Itk, a nonreceptor tyrosine kinase, is expressed in naive and activated T cells and is involved in T cell receptor (TCR) signaling where it phosphorylates Phospholipase-C gamma. Mutations affecting Itk impair TCR-induced Ca2+ mobilization and ERK activation. Itk is also involved in TCR-driven actin cytoskeleton reorganization and integrin adhesion regulation. Itk-deficient mice exhibit a decrease in peripheral T cells numbers, decreased T cell proliferation, and abnormal T cell phenotypes. Specifically, they show a 30-50% decrease in CD4 numbers and increased expression of activation/memory markers, particularly in CD8 cells, where almost all cells are CD8+CD44loCD122lo T cells and CD8+ T cells. They also exhibit defects in thymic development of CD8+CD44hiCD122hi. They also exhibit defects in thymic positive and negative selection and have abnormal ratios of splenic and thymic T and B cells. Itk-deficient mice show specific defects in responses to Th2-inducing immune challenges in vivo and show altered cytokine production in vivo and in vitro. Mice homozygous for this allele are viable and fertile.
A targeting vector was designed to insert a STOP codon in exon 2 and to replace exon 4 and part of exon 3 of the IL2 inducible T cell kinase (Itk) gene with a neomycin resistance (neo) cassette. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric males were bred to C57BL/6J females. These mice were backcrossed for 10 generations to C57BL/6J background. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.
Allele Name | targeted mutation 1, Dan R Littman |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | itk-; Itktm1Drl |
Gene Symbol and Name | Itk, IL2 inducible T cell kinase |
Gene Synonym(s) | |
Strain of Origin | 129S4/SvJae |
Chromosome | 11 |
Molecular Note | Exon 4 and part of exon 3 of this gene was replaced with a PGK(G)neopA cassette via homologous recombination. A stop codon was engineered at position 78 to further ensure a null allele. PCR and Southern blot analysis confirmed the presence of the targeted mutation, and Western blot analysis determined no Itk protein was present in thymocytes of homozygous mutant animals. |
When maintaining a live colony, homozygous mice may be bred together.
When using the B6.129S4-Itktm1Litt/PlsJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #024845 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous for Itk<tm1Litt> |
Frozen Mouse Embryo | B6.129S4-Itk<tm1Litt>/PlsJ Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.129S4-Itk<tm1Litt>/PlsJ Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.129S4-Itk<tm1Litt>/PlsJ Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | B6.129S4-Itk<tm1Litt>/PlsJ Frozen Embryo | $3373.50 |
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