Strain Detail Sheet

Strain Name    :

129S4-Ctla4tm1Shr Cd28tm1Shr/Mmnc

Stock Number :

030492-UNC

Gene Information

Gene Details [Including genotyping protocols]

(provided by MGI)
Allele Symbol: Ctla4tm1Shr
Name: targeted mutation 1, Arlene H Sharpe
Alteration at locus: Knockout
Allele Symbol: Cd28tm1Shr
Name: targeted mutation 1, Arlene H Sharpe
Alteration at locus: Knockout

Genetic Alterations:
neo cassette inserted into exon2 of ctla-4 and hygro cassette inserted into exon2 of cd28

Genotype Determination:

ES Cell Line: J1 derived from 129S4

Strain Description [Including phenotype, strain background, strain development and suggested control mice]

Phenotype

Homozygous phenotype: 1) Defective T cell activation 2) Can also be used to study B7-1: PD-L1 interactions

Heterozygous phenotype: None


Mammalian Phenotype Terms:(provided by MGI)      Extend all MPTs
      assigned by genotype

The following phenotype information may relate to one or more alleles on a genetic background differing from this MMRRC strain.
Ctla4tm1Shr/Ctla4+
        C.129S4-Cd28<tm1Shr> Ctla4<tm1Shr>
  • hematopoietic system phenotype
    • abnormal CD8-positive T cell morphology (MGI Ref ID J:125259)
      • abnormally high levels of CD5 (a marker of T cell activation) and CD8 expression on T cells
  • immune system phenotype
    • abnormal CD8-positive T cell morphology (MGI Ref ID J:125259)
      • abnormally high levels of CD5 (a marker of T cell activation) and CD8 expression on T cells
    • increased susceptibility to autoimmune disorder (MGI Ref ID J:125259)
Ctla4tm1Shr/Ctla4tm1Shr
        C.129S4-Cd28<tm1Shr> Ctla4<tm1Shr>
  • immune system phenotype
    • abnormal interferon level (MGI Ref ID J:68642)
      • upon secondary stimulation in vitro, interferon-gamma levels are increased relative to in wild-type cells
    • abnormal interleukin secretion (MGI Ref ID J:68642)
      • upon primary stimulation in vitro, IL-2 production is decreased by 50% relative to in wild-type cells
      • upon secondary stimulation in vitro, IL-4 and IL-10 production is decreased relative to in wild-type cells
    • decreased CD4-positive T cell number (MGI Ref ID J:68642)
      • the number of CD4+ CD69+ T cells is reduced by 50% compared to in wild-type mice
      • however, T and B cell development is normal
    • decreased T cell proliferation (MGI Ref ID J:68642)
      • in vitro T cell proliferation is reduced relative to wild-type cells
    • increased length of allograft survival (MGI Ref ID J:68642)
      • allograft survival is increased compared to in wild-type mice but mice eventually reject grafts
  • hematopoietic system phenotype
    • decreased CD4-positive T cell number (MGI Ref ID J:68642)
      • the number of CD4+ CD69+ T cells is reduced by 50% compared to in wild-type mice
      • however, T and B cell development is normal
    • decreased T cell proliferation (MGI Ref ID J:68642)
      • in vitro T cell proliferation is reduced relative to wild-type cells
  • homeostasis/metabolism phenotype
    • abnormal interferon level (MGI Ref ID J:68642)
      • upon secondary stimulation in vitro, interferon-gamma levels are increased relative to in wild-type cells

Strain of Origin: 129

Strain genetic background: 129

Strain Development: Strain generated from J1 embryonic stem cells; chimeras bred to 129S4/Sv Jae (same strain from which the J1 cells were generated).

Suggested Control Mice:

  • Wildtype littermates

Research Applications

  • Immunology and Inflammation

Strain Origin

Donor: Arlene H. Sharpe, M.D., Ph.D., Harvard Medical School

Primary Reference:

  • Mandelbrot DA, Oosterwegel MA, Shimizu K, Yamada A, Freeman GJ, Mitchell RN, Sayegh MH, Sharpe AH. B7-dependent T-cell costimulation in mice lacking CD28 and CTLA4. J Clin Invest. 2001 Apr;107(7):881-7. (Medline PMID: 11285307)
  • Butte MJ, Keir ME, Phamduy TB, Sharpe AH, Freeman GJ. Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity. 2007 Jul;27(1):111-22. Epub 2007 Jul 12. (Medline PMID: 17629517)

Colony and Husbandry Information

Special Considerations

Immunodeficient strain, so may want to use acidified water or antibiotics

Health Status Report

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email mmrrc_health@med.unc.edu.

Order Request Information

Availability Level

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

Conditions of Distribution [Including applicable technology transfer agreements]

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

The donor or their institution limits the distribution to non-profit institutions only.

Fees

Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # - Description Distribution
Fee/unit (US $)
Units Notes
030492-UNC-RESUSLitter recovered from cryo-archive
$2,022.00
Non-Profit
Litter Recovered litter1; additional fees for any special requests.

1 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

2 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

3 An aliquot contains a sufficient number of embryos (in one or more vials and based on the transfer success rate of the MMRRC facility) to transfer to at least two recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section above). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.



To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.



The MMRRC is a collaborative effort, funded by grants from DPCPSI of the NIH.

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