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 B6.129-Zap70tm1Weis/J    (Changed: 11-MAR-11 ) Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation ?+N1p (12-JUN-05) Generation Definitions   Donating Investigator Dr. Arthur Weiss,   University of California, San Francisco

Description
Mice that are homozygous null for the Zap70 gene are viable, fertile, and are immunodeficient. No Zap70 gene product (protein) is immunodetected in the thymocytes of homozygous mice. An intermediate level of expression was immunodetected in the thymocytes of heterozygous mice. Thymic development is arrested at the CD4+/CD8+ Double Positive stage. No peripheral T lymphocytes are detected. Fewer dendritic epidermal T cells were immunodetectable, and those present have an abnormal morphology. This mutant mouse strain represents a model that may be useful in studies related to a rare autosomal recessive form of human SCID as well as thymic development.

Development
A targeting vector containing neomycin resistance and thymidine kinase genes was used to delete approximately 2kb of the Zap70 gene sequence that encodes amino acids 221-520 and includes the C-terminal SH2 domain. The construct was transfected into 129X1/SvJ-derived JM1 embryonic stem cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were backcrossed to C57BL/6J.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Zap70

016096

B6.Cg-Tg(Zap70*M413A)2Weis/J

View Strains carrying other alleles of Zap70     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Selective T-Cell Defect; STCD   (ZAP70)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Zap70^tm1Weis/Zap70^tm1Weis

        involves: 129X1/SvJ * C57BL/6J

• immune system phenotype
• abnormal T cell differentiation
  • the number of dendritic epidermal T cells is reduced and those cells present lack the characteristic dendritic extensions   (MGI Ref ID J:74974)
  • few intestinal intraepithelial lymphocytes express gamma delta or alpha beta T cell receptors   (MGI Ref ID J:74974)
• • arrested T cell differentiation
    • arrest at the double positive stage   (MGI Ref ID J:74974)
• abnormal lymph node cell ratio
  • lymph nodes contain mostly B cells and a significant percentage of CD3+ (but CD4- and CD8-) cells which are primarily gamma delta T cells   (MGI Ref ID J:74974)
  • the percentage of gamma delta T cells is increased but the absolute number of these cell is similar to wild-type   (MGI Ref ID J:74974)
• abnormal splenic cell ratio
  • spleens are composed of mostly B cells   (MGI Ref ID J:74974)
• small lymph nodes   (MGI Ref ID J:74974)
• hematopoietic system phenotype
• abnormal T cell differentiation
  • the number of dendritic epidermal T cells is reduced and those cells present lack the characteristic dendritic extensions   (MGI Ref ID J:74974)
  • few intestinal intraepithelial lymphocytes express gamma delta or alpha beta T cell receptors   (MGI Ref ID J:74974)
• • arrested T cell differentiation
    • arrest at the double positive stage   (MGI Ref ID J:74974)
• abnormal splenic cell ratio
  • spleens are composed of mostly B cells   (MGI Ref ID J:74974)
• cellular phenotype
• abnormal T cell differentiation
  • the number of dendritic epidermal T cells is reduced and those cells present lack the characteristic dendritic extensions   (MGI Ref ID J:74974)
  • few intestinal intraepithelial lymphocytes express gamma delta or alpha beta T cell receptors   (MGI Ref ID J:74974)
• • arrested T cell differentiation
    • arrest at the double positive stage   (MGI Ref ID J:74974)

View Research Applications

Research Applications

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

Zap70^tm1Weis related

Immunology, Inflammation and Autoimmunity Research
Immunodeficiency
      T cell deficiency

Research Tools
Immunology and Inflammation Research
      T cell deficiency

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Zap70tm1Weis
Allele Name		targeted mutation 1, Arthur Weiss
Allele Type		Targeted (knock-out)
Common Name(s)		ZAP-70 -;
Mutation Made By		Theresa Kadlecek,   University of California, San Francisco
Strain of Origin		129X1/SvJ
ES Cell Line Name		JM-1
ES Cell Line Strain		129X1/SvJ
Gene Symbol and Name		Zap70, zeta-chain (TCR) associated protein kinase
Chromosome		1
Gene Common Name(s)		AI327364; SRK; STCD; STD; Srk; TZK; ZAP-70; expressed sequence AI327364; mr t-less; mrtle; mur; murdoch; syk related kinase;
Molecular Note		A neomycin resistance cassette replaced a genomic fragment containing sequences corresponding to amino acids 221 to 520, which encode the C-terminal SH2 domain. Western blot analysis on thymocytes derived from homozygous mice confirmed that no detectable protein is expressed from this allele. [MGI Ref ID J:74974]

Genotyping

Genotyping Information

Genotyping Protocols

Zap70^tm1Weisalternate1,

Separated MCA

Zap70^tm1Weis, Standard PCR
Zap70^tm1Weisalternate1, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Kadlecek TA; van Oers NS; Lefrancois L; Olson S; Finlay D; Chu DH; Connolly K; Killeen N; Weiss A. 1998. Differential requirements for ZAP-70 in TCR signaling and T cell development. J Immunol 161(9):4688-94. [PubMed: 9794398]  [MGI Ref ID J:74974]

Additional References

Sosinowski T; Killeen N; Weiss A. 2001. The Src-like adaptor protein downregulates the T cell receptor on CD4+CD8+ thymocytes and regulates positive selection. Immunity 15(3):457-66. [PubMed: 11567635]  [MGI Ref ID J:71804]

Zap70^tm1Weis related

Au-Yeung BB; Levin SE; Zhang C; Hsu LY; Cheng DA; Killeen N; Shokat KM; Weiss A. 2010. A genetically selective inhibitor demonstrates a function for the kinase Zap70 in regulatory T cells independent of its catalytic activity. Nat Immunol 11(12):1085-92. [PubMed: 21037577]  [MGI Ref ID J:167326]

Clarke RL; Thiemann S; Refaeli Y; Werlen G; Potter TA. 2009. A new function for LAT and CD8 during CD8-mediated apoptosis that is independent of TCR signal transduction. Eur J Immunol 39(6):1619-31. [PubMed: 19449311]  [MGI Ref ID J:149450]

Colucci F; Schweighoffer E; Tomasello E; Turner M; Ortaldo JR; Vivier E; Tybulewicz VL; Di Santo JP. 2002. Natural cytotoxicity uncoupled from the Syk and ZAP-70 intracellular kinases. Nat Immunol 3(3):288-94. [PubMed: 11836527]  [MGI Ref ID J:74994]

Fallah-Arani F; Schweighoffer E; Vanes L; Tybulewicz VL. 2008. Redundant role for Zap70 in B cell development and activation. Eur J Immunol 38(6):1721-33. [PubMed: 18465772]  [MGI Ref ID J:136323]

Gong Q; Jin X; Akk AM; Foger N; White M; Gong G; Wardenburg JB; Chan AC. 2001. Requirement for tyrosine residues 315 and 319 within zeta chain-associated protein 70 for T cell development. J Exp Med 194(4):507-18. [PubMed: 11514606]  [MGI Ref ID J:71098]

Jakob T; Kollisch GV; Howaldt M; Bewersdorff M; Rathkolb B; Muller ML; Sandholzer N; Nitschke L; Schiemann M; Mempel M; Ollert M; Neubauer A; Soewarto DA; Kremmer E; Ring J; Behrendt H; Flaswinkel H. 2008. Novel mouse mutants with primary cellular immunodeficiencies generated by genome-wide mutagenesis. J Allergy Clin Immunol 121(1):179-184.e7. [PubMed: 17767948]  [MGI Ref ID J:137446]

Lee WH; Ramos T; Krymskaya L; Liu CP. 2003. Development of T cells expressing an altered TCR complex. Eur J Immunol 33(10):2696-705. [PubMed: 14515253]  [MGI Ref ID J:115654]

Mingueneau M; Sansoni A; Gregoire C; Roncagalli R; Aguado E; Weiss A; Malissen M; Malissen B. 2008. The proline-rich sequence of CD3epsilon controls T cell antigen receptor expression on and signaling potency in preselection CD4+CD8+ thymocytes. Nat Immunol 9(5):522-32. [PubMed: 18408722]  [MGI Ref ID J:134506]

Myers MD; Dragone LL; Weiss A. 2005. Src-like adaptor protein down-regulates T cell receptor (TCR)-CD3 expression by targeting TCRzeta for degradation. J Cell Biol 170(2):285-94. [PubMed: 16027224]  [MGI Ref ID J:100141]

Myers MD; Sosinowski T; Dragone LL; White C; Band H; Gu H; Weiss A. 2006. Src-like adaptor protein regulates TCR expression on thymocytes by linking the ubiquitin ligase c-Cbl to the TCR complex. Nat Immunol 7(1):57-66. [PubMed: 16327786]  [MGI Ref ID J:112388]

Palacios EH; Weiss A. 2007. Distinct roles for Syk and ZAP-70 during early thymocyte development. J Exp Med 204(7):1703-15. [PubMed: 17606633]  [MGI Ref ID J:125879]

Saini M; Sinclair C; Marshall D; Tolaini M; Sakaguchi S; Seddon B. 2010. Regulation of Zap70 expression during thymocyte development enables temporal separation of CD4 and CD8 repertoire selection at different signaling thresholds. Sci Signal 3(114):ra23. [PubMed: 20332428]  [MGI Ref ID J:165067]

Sosinowski T; Killeen N; Weiss A. 2001. The Src-like adaptor protein downregulates the T cell receptor on CD4+CD8+ thymocytes and regulates positive selection. Immunity 15(3):457-66. [PubMed: 11567635]  [MGI Ref ID J:71804]

White AJ; Nakamura K; Jenkinson WE; Saini M; Sinclair C; Seddon B; Narendran P; Pfeffer K; Nitta T; Takahama Y; Caamano JH; Lane PJ; Jenkinson EJ; Anderson G. 2010. Lymphotoxin signals from positively selected thymocytes regulate the terminal differentiation of medullary thymic epithelial cells. J Immunol 185(8):4769-76. [PubMed: 20861360]  [MGI Ref ID J:164718]

Health & husbandry

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.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & Husbandry	This strain originated and is maintained on a B6;129X background and has been crossed to C57BL/6 at least five times before being made homozygous. Homozygous mice are more susceptible to pathogenic bacteria so conventional specific pathogen-free (SPF) conditions and occasional prophylactic antibiotic treatment are recommended by donating investigator.
Diet Information	LabDiet® 5K52/5K67

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
	000664 C57BL/6J
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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