Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names 129/Sv-Csktm1Sor/J    (Changed: 14-NOV-12 ) Type Coisogenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation F?+1 Generation Definitions   Donating Investigator Dr. Philippe Soriano,   Mount Sinai School of Medicine

Description
Mice homozygous for disruption of the csk gene die in utero at 9 - 10 days of gestation, exhibiting defects in neurulation. Mutant embryos are anatomically indistinguishable from normal or heterozygous littermates at E8.5, but are identifiable at E9.5 by their smaller size, failure to 'turn' (reverse orientation of germ layers) and failure to close their cephalic neural folds. The allantois of these mutant embryos is also abnormal and does not connect with the chorion, preventing formation of the umbilical cord and placenta. The kinase Csk plays a role in negative regulation of the Src family tyrosine kinases by phosphorylating a key carboxy-terminal tyrosine residue. Expression of csk in normal embryos is detectable at low levels beginning at E8.5, and is at its highest level of expression at E9.5.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Csk

018320

B6.129P2-Csktm1Tara/J

View Strains carrying other alleles of Csk     (1 strain)

Additional Web Information

New 129 Nomenclature Bulletin

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Csk^tm1Sor/Csk⁺

        129P2.129S7-Csk^tm1Sor

• behavior/neurological phenotype
• abnormal food preference
  • given a chose of two novel food sources they choose a food they have already seen another mouse eat   (MGI Ref ID J:188631)
• abnormal object recognition memory
  • no increased investigation of displaced familiar objects, similar to 129P2 control but unlike C57BL/6 control   (MGI Ref ID J:188631)
• abnormal social investigation
  • increased social approach of a strange mouse as opposed to investigating an empty cage or examining a pre-exposed familiar mouse   (MGI Ref ID J:188631)
  • less time is spent re-investigating a strange mouse during second exposure to that mouse   (MGI Ref ID J:188631)
  • given a chose of two novel food sources they choose a food they have already seen another mouse eat   (MGI Ref ID J:188631)
• decreased anxiety-related response
  • increased time spent exploring open arms of an elevated + maze   (MGI Ref ID J:188631)

Csk^tm1Sor/Csk^tm1Sor

        either: (involves: 129S7/SvEvBrd) or (involves: 129S7/SvEvBrd * C57BL/6J)

• mortality/aging
• complete embryonic lethality during organogenesis
  • most homozygotes die between E9.5 and E10.5   (MGI Ref ID J:12622)
  • no homozygotes are recovered at or after E11.5   (MGI Ref ID J:12622)
• embryogenesis phenotype
• abnormal allantois morphology
  • at E9.5, the allantois is often abnormal and either resorbing or tuberous   (MGI Ref ID J:12622)
• • enlarged allantois
    • allantois is often overgrown with a "bleb" at its extremity   (MGI Ref ID J:12622)
• absent notochord
  • at E8.5, the mutant notochord is consistently smaller or even absent   (MGI Ref ID J:12622)
• caudal body truncation
  • at E9.5, homozygotes exhibit a small and underdeveloped caudal portion   (MGI Ref ID J:12622)
• decreased embryo size
  • at E9.5, most homozygous mutant embryos are ~25% to ~50% the size of wild-type embryos   (MGI Ref ID J:12622)
• incomplete cephalic closure
  • at E9.5, homozygotes fail to close their cephalic neural folds   (MGI Ref ID J:12622)
• incomplete embryo turning
  • at E9.5, most homozygous mutant embryos remain unturned   (MGI Ref ID J:12622)
• open neural tube
  • at E9.5, the mutant neural tube is closed at the level of the otic vesicle but remains open beyond the midbrain-forebrain boundary   (MGI Ref ID J:12622)
  • abnormal folding of the neuroectoderm is noted at the level of the cephalic folds and of the neural tube   (MGI Ref ID J:12622)
• wavy neural tube
  • at E9.5, homozygotes exhibit a wavy and disorganized neural tube   (MGI Ref ID J:12622)
  • in addition, the neural tube is often curved and infiltrated with pyknotic cells   (MGI Ref ID J:12622)
• nervous system phenotype
• incomplete cephalic closure
  • at E9.5, homozygotes fail to close their cephalic neural folds   (MGI Ref ID J:12622)
• open neural tube
  • at E9.5, the mutant neural tube is closed at the level of the otic vesicle but remains open beyond the midbrain-forebrain boundary   (MGI Ref ID J:12622)
  • abnormal folding of the neuroectoderm is noted at the level of the cephalic folds and of the neural tube   (MGI Ref ID J:12622)
• wavy neural tube
  • at E9.5, homozygotes exhibit a wavy and disorganized neural tube   (MGI Ref ID J:12622)
  • in addition, the neural tube is often curved and infiltrated with pyknotic cells   (MGI Ref ID J:12622)
• growth/size phenotype
• decreased embryo size
  • at E9.5, most homozygous mutant embryos are ~25% to ~50% the size of wild-type embryos   (MGI Ref ID J:12622)
• cardiovascular system phenotype
• poor circulation
  • at E9.5, blood circulation is essentially absent in the visceral yolk sac and in mutant embryos   (MGI Ref ID J:12622)
  • however, all homozygotes at this stage show normal decidual sizes and normal beating of the heart   (MGI Ref ID J:12622)
• craniofacial phenotype
• megacephaly
  • at E9.5, homozygotes display a disproportionately bulky and dilated head   (MGI Ref ID J:12622)

View Research Applications

Research Applications

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

Csk^tm1Sor 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 (knock-out)
Common Name(s)		Csk-;
Mutation Made By		Dr. Philippe Soriano,   Mount Sinai School of Medicine
Strain of Origin		129S7/SvEvBrd-Hprt<+>
ES Cell Line Name		AB1
ES Cell Line Strain		129S7/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]

Genotyping

Genotyping Information

Genotyping Protocols

Csk^tm1Sor,

Separated MCA

Csk^tm1Sor, Separated PCR
Csk^tm1Sor, Standard PCR
NEOTD (Generic Neo), Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

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]

Additional References

Csk^tm1Sor 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]

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

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

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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.

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