Strain Name:

B6.129X1-Zap70tm1Weis/J

Stock Number:

004225

Order this mouse

Availability:

Cryopreserved - Ready for recovery

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.
Specieslaboratory mouse
 
Donating InvestigatorDr. 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 is associated with a similar, but not exact match to this JAX® Mice strain.

Zap70tm1Weis/Zap70tm1Weis

        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)
View Research Applications

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

Zap70tm1Weis related

Immunology, Inflammation and Autoimmunity Research
Immunodeficiency
      T cell deficiency

Research Tools
Immunology, Inflammation and Autoimmunity 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 (Null/Knockout)
Common Name(s) ZAP-70 -;
Mutation Made By Theresa Kadlecek,   University of California, San Francisco
Strain of Origin129X1/SvJ
ES Cell Line NameJM-1
ES Cell Line Strain129X1/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

Generic Neo Quantitative PCR-QPCR- 1.2, QPCR
Zap70tm1Weisalternate1,

Separated MCA


Zap70tm1Weis, Standard PCR
Zap70tm1Weisalternate1, 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]

Zap70tm1Weis 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 & HusbandryThis 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.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


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

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2525.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We willfulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3283.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We willfulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

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

Payment Terms and Conditions

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.


See Terms of Use tab for General Terms and Conditions


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.
Ordering Information
JAX® Mice
Surgical and Preconditioning Services
JAX® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use


General Terms and Conditions


Contact information

General inquiries regarding Terms of Use

Contracts Administration

phone:207-288-6470

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED “AS IS”. JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.


(6.6)