Strain Name:

B6.Cg-Csktm1Sor Tg(Csk*)2Weis/WeisJ

Stock Number:

025250

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Availability:

Under Development - Now Accepting Orders

Estimated Available for Distribution Date: 23-FEB-15
Use Restrictions Apply, see Terms of Use
These CskAS mice express a conditionally inhibitory CSK protein and lack endogenous CSK expression. They may be useful for studying the requirements of Csk on the control of TCR signaling.

Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Transgenic;
Additional information on Genetically Engineered and Mutant Mice.
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Additional information on Congenic nomenclature.
Mating System
Specieslaboratory mouse
GenerationN13+pN1
Generation Definitions
 
Donating InvestigatorDr. Arthur Weiss,   University of California, San Francisco

Description
Mice hemizygous for the BAC CskAS transgene are viable and fertile. These mice do not express the endogenous c-src tyrosine kinase (CSK) protein. These mice do express mutant CSK, from the BAC transgene, which contains a point mutation at position 266 resulting in a threonine to glycine mutation. This mutation creates a larger ATP-binding pocket in the expressed protein, allowing for specific and rapid inhibition by an analog of the kinase inhibitor PP1, 3-iodo-benzyl-PP1 (3-IB-PP1). CSK is a cytosolic tyrosine-protein kinase that plays a role in the regulation of cell growth, differentiation, migration and immune response. CSK phosphorylates tyrosine residues located in the C-terminal tails of Src-family kinases (SFKs), which in turn suppress signaling by surface receptors including T-cell receptor (TCR) and B-cell receptor (BCR). CskAS mice have 2.5-fold as much expression of CSK as wild-type mice and display normal T cell development. Inhibition of CSK with 3-IB-PP1 in thymocytes induces activation of SFKs and proximal TCR signaling. Defects in inositol phosphates, intracellular calcium, and phosphorylation of Erk are also seen, although remodeling of the actin cytoskeleton is sufficient to reverse these defects and to allow full TCR signaling. Mice hemizygous for the CSK* transgene and homozygous for Csktm1Sor allele are viable and fertile. The Csktm1Sor allele alone is homozygous embryonic lethal. The donating investigator has not tried to make CSK* transgenic homozygous mice.

Development
Bacterial artificial chromosome (BAC) library (CHORI) was used to obtain a BAC (#RP24-400B5) containing the entire mouse Csk (c-src tyrosine kinase) gene. A point mutation was introduced in Csk at position 266 resulting in a threonine to glycine mutation, inducing a larger ATP-binding pocket to be formed in the expressed protein. To inactivate other genes present in the BAC, both ends of the BAC were deleted, leaving 74kb of sequence, and an in-frame stop codon was inserted in exon 2 of Lman1l (lectin, mannose-binding 1 like) gene. This BAC was microinjected into fertilized C57BL/6 oocytes. CskAS mice from founder line 2 were maintained by breeding transgenic mice with mice carrying the Csktm1Sor/J allele that have been bred to C57BL/6 mice for at least 13 generations (similar to Stock No. 003201). These mice were maintained on a C57BL/6 background. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   Csktm1Sor allele
003201   129S-Csktm1Sor/J
View Strains carrying   Csktm1Sor     (1 strain)

Strains carrying other alleles of Csk
018320   B6.129P2-Csktm1Tara/J
View Strains carrying other alleles of Csk     (1 strain)

Phenotype

Phenotype Information

View Research Applications

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

Immunology, Inflammation and Autoimmunity Research
T Cell Receptor Signaling Defects

Csktm1Sor related

Cancer Research
Genes Regulating Growth and Proliferation

Cell Biology Research
Genes Regulating Growth and Proliferation

Developmental Biology Research
Embryonic Lethality (Homozygous)
Neural Tube Defects
Postnatal Lethality

Neurobiology Research
Neural Tube Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Csktm1Sor
Allele Name targeted mutation 1, Philippe Soriano
Allele Type Targeted (Null/Knockout)
Common Name(s) Csk-;
Mutation Made ByDr. Philippe Soriano,   Mount Sinai School of Medicine
Strain of Origin129S7/SvEvBrd-Hprt<+>
ES Cell Line NameAB1
ES Cell Line Strain129S7/SvEvBrd-Hprt<+>
Gene Symbol and Name Csk, c-src tyrosine kinase
Chromosome 9
Gene Common Name(s) AW212630; expressed sequence AW212630;
Molecular Note Deletion of all coding sequences and replacement with a neomycin cassette. [MGI Ref ID J:12622]
 
Allele Symbol Tg(Csk*)2Weis
Allele Name transgene insertion 2, Arthur Weiss
Allele Type Transgenic (Inserted expressed sequence)
Common Name(s) CskAS;
Strain of OriginC57BL/6
Expressed Gene Csk, c-src tyrosine kinase, mouse, laboratory
Molecular Note A bacterial artificial chromosome (BAC) library from CHORI was used to obtain a BAC (#RP24-400B5) containing the entire mouse Csk (c-src tyrosine kinase) gene. A point mutation was introduced in Csk at position 266 resulting in a threonine to glycine mutation, inducing a larger ATP-binding pocket to be formed in the expressed protein. To inactivate other genes present in the BAC, both ends of the BAC were deleted, leaving 74kb of sequence, and an in-frame stop codon was inserted in exon 2 of Lman1l (lectin, mannose-binding 1 like) gene. [MGI Ref ID J:208674]
 

Genotyping

Genotyping Information

Genotyping Protocols

Csktm1Sor,

Separated MCA


Tg(Csk*)2Weis, End Point Analysis


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Tan YX; Manz BN; Freedman TS; Zhang C; Shokat KM; Weiss A. 2014. Inhibition of the kinase Csk in thymocytes reveals a requirement for actin remodeling in the initiation of full TCR signaling. Nat Immunol 15(2):186-94. [PubMed: 24317039]  [MGI Ref ID J:208674]

Additional References

Csktm1Sor related

Duan LJ; Imamoto A; Fong GH. 2004. Dual roles of the C-terminal Src kinase (Csk) during developmental vascularization. Blood 103(4):1370-2. [PubMed: 14576066]  [MGI Ref ID J:115663]

Imamoto A; Soriano P. 1993. Disruption of the csk gene, encoding a negative regulator of Src family tyrosine kinases, leads to neural tube defects and embryonic lethality in mice. Cell 73(6):1117-24. [PubMed: 7685657]  [MGI Ref ID J:12622]

Sinai L; Mathew R; Roder JC. 2012. Impaired social memories in 129P2 inbred mice are rescued by reduced Csk expression. Genes Brain Behav 11(5):559-67. [PubMed: 22348736]  [MGI Ref ID J:188631]

Thomas SM; Soriano P; Imamoto A. 1995. Specific and redundant roles of Src and Fyn in organizing the cytoskeleton. Nature 376(6537):267-71. [PubMed: 7617039]  [MGI Ref ID J:113005]

Zikherman J; Jenne C; Watson S; Doan K; Raschke W; Goodnow CC; Weiss A. 2010. CD45-Csk phosphatase-kinase titration uncouples basal and inducible T cell receptor signaling during thymic development. Immunity 32(3):342-54. [PubMed: 20346773]  [MGI Ref ID J:158876]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, mice hemizygous for the CSK* transgene and homozygous for Csktm1Sor may be bred to mice heterozygous for Csktm1Sor, or to wildtype mice from the colony, or to C57BL/6J (Stock No. 000664). The Csk allele alone is homozygous embryonic lethal. The donating investigator has not tried to make CSK* transgenic homozygous mice.
Mating System

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


 

This strain is currently Under Development - Now Accepting Orders.
Estimated Available for Distribution Date: 23-FEB-15

Please note: You may now place orders for this strain although it is not yet ready for distribution. Estimated available for distribution dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for distribution depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain.

Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $232.00Female or MaleHeterozygous for Csk, Noncarrier for Tg(Csk*)2Weis  
$232.00Female or MaleHeterozygous for Csk, Hemizygous for Tg(Csk*)2Weis  
Individual Mouse $232.00Female or MaleHomozygous for Csk, Hemizygous for Tg(Csk*)2Weis  
Price per Pair (US dollars $)Pair Genotype
$464.00Heterozygous for Csk, Noncarrier x Homozygous for Csk, Hemizygous for Tg(Csk*)2Weis  
$464.00Homozygous for Csk, Hemizygous for Tg(Csk*)2Weis x Heterozygous for Csk, Noncarrier  

Standard Supply

Under Development - Now Accepting Orders The strain development process (i.e. importation, rederivation, and colony expansion) usually takes six to nine months.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $301.60Female or MaleHeterozygous for Csk, Noncarrier for Tg(Csk*)2Weis  
$301.60Female or MaleHeterozygous for Csk, Hemizygous for Tg(Csk*)2Weis  
Individual Mouse $301.60Female or MaleHomozygous for Csk, Hemizygous for Tg(Csk*)2Weis  
Price per Pair (US dollars $)Pair Genotype
$603.20Heterozygous for Csk, Noncarrier x Homozygous for Csk, Hemizygous for Tg(Csk*)2Weis  
$603.20Homozygous for Csk, Hemizygous for Tg(Csk*)2Weis x Heterozygous for Csk, Noncarrier  

Standard Supply

Under Development - Now Accepting Orders The strain development process (i.e. importation, rederivation, and colony expansion) usually takes six to nine months.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Under Development - Now Accepting Orders The strain development process (i.e. importation, rederivation, and colony expansion) usually takes six to nine months.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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