Overview

Itk^-/- mice may be useful for studying the role of ITK in the proliferation and activation of lymphocytes.

Donating Investigator

Pamela L Schwartzberg, National Human Genome Research Institute, National Institutes of Health (NHGRI, NIH)

Genetic overview

Genetic Background	Generation

Itk^tm1Litt

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Itk	IL2 inducible T cell kinase

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Research Applications

Cell Biology Research
Immunology, Inflammation and Autoimmunity Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

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⁺CD44^loCD122^lo T cells and CD8⁺ T cells. They also exhibit defects in thymic development of CD8⁺CD44^hiCD122^hi. 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.

Development

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.

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Liao XC; Littman DR. 1995. Altered T cell receptor signaling and disrupted T cell development in mice lacking Itk. Immunity 3(6):757-69PubMed: 8777721 MGI: J:31230

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Genetics

Itk^tm1Litt

Allele Symbol: Itk^tm1Litt

Allele Name	targeted mutation 1, Dan R Littman
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	itk^-; Itk^tm1Drl
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.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Cell Biology Research
- Defects in Cell Adhesion Molecules
- Defects in Extracellular Matrix Molecules
Immunology, Inflammation and Autoimmunity Research
- Lymphoid Tissue Defects
- Intracellular Signaling Molecules
- T Cell Receptor Signaling Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Itk^tm1Litt/Itk^tm1Litt
involves: 129S4/SvJae * C57BL/6

immune system phenotype

abnormal thymus cell ratio
- slight increase in number of CD24^hi CD8 SP thymocytes is seen relative to wild-type thymi; absolute number of CD24^int CD8 SP thymocytes is decreased to <50% of wild-type thymi
- absolute number of CD122^hi cells are increased in number at all stages of T cell development compared to wild-type
- at mature CD40^lo stage, thymi contain essentially no CD122^lo CD8 SP T cells
- CD24^lo CD8 SP thymocytes which are considered mature show an increase in number relative to wild-type
- number of CD8 single-positive thymocytes is increased relative to wild-type at 3 weeks of age

abnormal CD8-positive, alpha-beta T cell differentiation
- defects in thymic development of CD44^loCD122^loCD8+ T cells are detected

decreased CD8-positive, alpha-beta T cell number
- in blood, mice lack CD8+CD44^loCD122^lo T cells and total CD8+ T cell number is reduced to 20-30% compared to wild-type

endocrine/exocrine gland phenotype

abnormal thymus cell ratio
- CD24^lo CD8 SP thymocytes which are considered mature show an increase in number relative to wild-type
- absolute number of CD122^hi cells are increased in number at all stages of T cell development compared to wild-type
- number of CD8 single-positive thymocytes is increased relative to wild-type at 3 weeks of age
- slight increase in number of CD24^hi CD8 SP thymocytes is seen relative to wild-type thymi; absolute number of CD24^int CD8 SP thymocytes is decreased to <50% of wild-type thymi
- at mature CD40^lo stage, thymi contain essentially no CD122^lo CD8 SP T cells

hematopoietic system phenotype

abnormal thymus cell ratio
- absolute number of CD122^hi cells are increased in number at all stages of T cell development compared to wild-type
- slight increase in number of CD24^hi CD8 SP thymocytes is seen relative to wild-type thymi; absolute number of CD24^int CD8 SP thymocytes is decreased to <50% of wild-type thymi
- at mature CD40^lo stage, thymi contain essentially no CD122^lo CD8 SP T cells
- CD24^lo CD8 SP thymocytes which are considered mature show an increase in number relative to wild-type
- number of CD8 single-positive thymocytes is increased relative to wild-type at 3 weeks of age

decreased CD8-positive, alpha-beta T cell number
- in blood, mice lack CD8+CD44^loCD122^lo T cells and total CD8+ T cell number is reduced to 20-30% compared to wild-type

abnormal CD8-positive, alpha-beta T cell differentiation
- defects in thymic development of CD44^loCD122^loCD8+ T cells are detected

Genotype: Itk^tm1Litt/Itk^tm1Litt
involves: 129S4/SvJae

cellular phenotype

decreased T cell proliferation
- mice show variable defects in CD4+ T cell proliferation

hematopoietic system phenotype

decreased T cell proliferation
- mice show variable defects in CD4+ T cell proliferation

immune system phenotype

increased susceptibility to parasitic infection
- mice infected with Toxoplasma gondii survive the early infection which requires natural killer cells; mean survival time of 69 days

decreased T cell proliferation
- mice show variable defects in CD4+ T cell proliferation

Genotype: Itk^tm1Litt/Itk^tm1Litt
involves: 129S4/SvJae * C57BL/6J

immune system phenotype

decreased B cell number
- number of B cells is increased in concert with reduction of T cell numbers

decreased CD4-positive, alpha beta T cell number
- ratio of CD4 single positive thymocytes versus CD8 SP thymocytes is reduced 2-3-fold compared to heterozygous or wild-type littermates
- number and proportion of CD4+ T cells in periphery show a more marked reduction than CD8+ T cells

decreased T cell number
- number of T cells is reduced by 1.5- to 2-fold compared to controls

decreased T cell proliferation
- CD4+ T cells stimulated with concanavalin A or anti-CD3 antibodies in presence of syngeneic splenocytes show reduced proliferative responses indicating early phase of TCR-mediated signaling is compromised
- in response to allogeneic stimulation, lymph node CD4+ T cells show significantly reduced proliferation in a mixed lymphocyte reaction compared to control littermates
- CD4+ and CD8+ cells challenged with irradiated splenocytes from MHC class I or class II mutant mouse strains display significantly reduced proliferation compared to controls

mammalian phenotype

immune system phenotype
- Normal - cell numbers in lymph nodes and spleen are unchanged relative to controls

cellular phenotype

decreased T cell proliferation
- in response to allogeneic stimulation, lymph node CD4+ T cells show significantly reduced proliferation in a mixed lymphocyte reaction compared to control littermates
- CD4+ and CD8+ cells challenged with irradiated splenocytes from MHC class I or class II mutant mouse strains display significantly reduced proliferation compared to controls
- CD4+ T cells stimulated with concanavalin A or anti-CD3 antibodies in presence of syngeneic splenocytes show reduced proliferative responses indicating early phase of TCR-mediated signaling is compromised

hematopoietic system phenotype

decreased T cell number
- number of T cells is reduced by 1.5- to 2-fold compared to controls

decreased T cell proliferation
- CD4+ and CD8+ cells challenged with irradiated splenocytes from MHC class I or class II mutant mouse strains display significantly reduced proliferation compared to controls
- in response to allogeneic stimulation, lymph node CD4+ T cells show significantly reduced proliferation in a mixed lymphocyte reaction compared to control littermates
- CD4+ T cells stimulated with concanavalin A or anti-CD3 antibodies in presence of syngeneic splenocytes show reduced proliferative responses indicating early phase of TCR-mediated signaling is compromised

decreased CD4-positive, alpha beta T cell number
- ratio of CD4 single positive thymocytes versus CD8 SP thymocytes is reduced 2-3-fold compared to heterozygous or wild-type littermates
- number and proportion of CD4+ T cells in periphery show a more marked reduction than CD8+ T cells

decreased B cell number
- number of B cells is increased in concert with reduction of T cell numbers

The following phenotype relates to a compound genotype created using this strain

Genotype: Itk^tm1Litt/Itk^tm1Litt
B6.129S4-Itk

cellular phenotype

decreased T cell proliferation
- in response to loading with CFSE followed by stimulation with anti-CD3

hematopoietic system phenotype

abnormal positive T cell selection
- TCR dependent Ca2+ mobilization is reduced

decreased T cell proliferation
- in response to loading with CFSE followed by stimulation with anti-CD3

increased double-negative T cell number

decreased T cell number
- decrease in the number of peripheral T cells

abnormal T cell morphology
- most remaining single positive T cells have an activated/memory like phenotype

immune system phenotype

abnormal positive T cell selection
- TCR dependent Ca2+ mobilization is reduced

decreased interleukin-2 secretion
- in response to anti-CD3 anti-CD28 costimulation

decreased T cell number
- decrease in the number of peripheral T cells

increased double-negative T cell number

abnormal T cell morphology
- most remaining single positive T cells have an activated/memory like phenotype

decreased T cell proliferation
- in response to loading with CFSE followed by stimulation with anti-CD3

References

Liao XC; Littman DR. 1995. Altered T cell receptor signaling and disrupted T cell development in mice lacking Itk. Immunity 3(6):757-69PubMed: 8777721 MGI: J:31230

Additional - Itk^tm1Litt related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Itk
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, homozygous mice may be bred together.
- Additional Breeding and Husbandry Support
Mating System
- Heterozygote x Heterozygote
Citation
When using the B6.129S4-Itk^tm1Litt/PlsJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #024845 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
> >	Heterozygous for Itk<tm1Litt>

Related Products and Services

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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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

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.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Itktm1Litt

Allele Symbol: Itktm1Litt

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Itktm1Litt/Itktm1Littinvolves: 129S4/SvJae * C57BL/6

immune system phenotype

endocrine/exocrine gland phenotype

hematopoietic system phenotype

Genotype: Itktm1Litt/Itktm1Littinvolves: 129S4/SvJae

cellular phenotype

hematopoietic system phenotype

immune system phenotype

Genotype: Itktm1Litt/Itktm1Littinvolves: 129S4/SvJae * C57BL/6J

immune system phenotype

mammalian phenotype

cellular phenotype

hematopoietic system phenotype

Genotype: Itktm1Litt/Itktm1LittB6.129S4-Itk

cellular phenotype

hematopoietic system phenotype

immune system phenotype

References

Additional - Itktm1Litt related

Genotyping Protocols

Breeding Considerations

Mating System

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Itk^tm1Litt

Allele Symbol: Itk^tm1Litt

Genotype: Itk^tm1Litt/Itk^tm1Litt
involves: 129S4/SvJae * C57BL/6

Genotype: Itk^tm1Litt/Itk^tm1Litt
involves: 129S4/SvJae

Genotype: Itk^tm1Litt/Itk^tm1Litt
involves: 129S4/SvJae * C57BL/6J

Genotype: Itk^tm1Litt/Itk^tm1Litt
B6.129S4-Itk

Additional - Itk^tm1Litt related