Strain Detail Sheet

Strain Name    :

C57BL/6J-Card11m1Btlr/Mmucd

Stock Number :

030114-UCD

Other Names   :

king, C57BL/6J-Card11m1Btlr/Mmcd

Gene Information

Gene Details [Including genotyping protocols]

(provided by MGI)
Allele Symbol: Card11m1Btlr
Name: mutation 1, Bruce Beutler
Chromosome: 5
Alteration at locus: Chemically Induced
Gene Symbol: Card11
Name: caspase recruitment domain family, member 11
Chromosome: 5
Alteration at locus: Chemically Induced

Genetic Alterations:
ENU-induced A to T transversion at position 1791 of the Carma1/Card11 gene, in exon 12.

Genotype Determination:

ES Cell Line: Not Applicable

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

Phenotype

Homozygous phenotype: -No CD8+ T cell response after immunization and subsequent challenge with antigen- specific targets. - No interferon-gamma production by CD8+ T cells after immunization and stimulation with antigen in vitro. - No proliferation or CD25 upregulation after T cell receptor stimulation of T cells. - No CD4+Foxp3+ regulatory T cells in thymus, and greatly reduced numbers in spleen. - Reduced basal serum immunoglobulin levels. - Impaired B cell proliferation. - No antigen-specific IgG responses after immunization with ovalbumin. - Reduced numbers and percentages of natural killer (NK), NKT, gamma/delta T, memory CD4+ T, and mature B cells.

Heterozygous phenotype:


Mammalian Phenotype Terms:(provided by MGI)      Extend all MPTs
      assigned by genotype
Card11m1Btlr/Card11m1Btlr
        C57BL/6J-Card11<m1Btlr>
  • immune system phenotype
    • immune system phenotype (MGI Ref ID J:139069)
      • antigen presentation by CD8+ T cells is normal
      • upregulation of CD69 and CD44 by mutant T cells in response to treatment with TCR-crosslinking antibodies is only slightly impaired (nearly normal)
      • numbers and proportions of macrophages and neutrophils are normal
      • dendritic cell (DC) numbers and proportions appear normal; cross-priming by DCs is normal, and DCs from mutant mice upregulate costimulatory molecules (CD40, CD80, CD86, MHC class I and II) normally upon stimulation by apoptotic cells or toll-like receptor (TLR) ligands
      • abnormal CD4-positive, CD25-positive, alpha-beta regulatory T cell morphology (MGI Ref ID J:149767)
        • regulatory T cells fail to develop when mutant bone marrow is transferred to wild-type mice suggesting defect is intrinsic to hematopoietic pre-cursors
        • in vitro, less activated CD4+ T cells express the regulatory marker FoxP3
      • abnormal NK cell physiology (MGI Ref ID J:139069)
        • mutant mice fail to kill syngeneic class I MHC-deficient cells (NK cell-specific target cells) injected a week after primary immunization with irradiated ovalbumin (OVA)-expressing cells
      • abnormal T cell activation (MGI Ref ID J:139069)
        • in response to treatment with TCR-crosslinking antibodies (alpha-CD3/28), mutant T cells fail to upregulate CD25 (IL-2Ralpha chain), indicating impairment of TCR-mediated T cell activation
        • decreased T cell proliferation (MGI Ref IDs J:139069, J:149767)
          • (MGI Ref ID J:149767)
          • in response to treatment with TCR-crosslinking antibodies (alpha-CD3/28), mutant T cells fail to proliferate, indicating impairment of the TCR-mediated T cell proliferation response; the proliferation de fect can be partially rescued by IL-2 treatment of mutant T cells (MGI Ref ID J:139069)
          • in vitro-expanded CD8+ T cells isolated from mutant mice a week after their immunization with irradiated ovalbumin (OVA) expressing cells fail to undergo secondary expansion upon restimulation (MGI Ref ID J:139069)
      • abnormal cytokine secretion (MGI Ref ID J:149767)
        • while present in reduced numbers, TGF-beta secretion is enhanced in regulatory T cells
        • decreased interferon-gamma secretion (MGI Ref ID J:139069)
          • in vitro-expanded CD8+ T cells isolated from mutant mice a week after their immunization with irradiated ovalbumin (OVA) expressing cells fail to produce interferon (IFN) gamma upon restimulation
        • decreased interleukin-2 secretion (MGI Ref ID J:139069)
          • mutant T cells do not produce interleukin 2 (IL-2) in response to treatment with TCR-crosslinking antibodies (alpha-CD3/28)
      • abnormal cytotoxic T cell physiology (MGI Ref ID J:139069)
        • mutant mice immunized with irradiated ovalbumin (OVA) expressing cells fail to kill OVA (specific antigen) expressing target C57BL/6J splenocytes injected a week later
      • abnormal double-negative T cell morphology (MGI Ref IDs J:139069, J:149767)
        • (MGI Ref ID J:149767)
        • the double-negative thymocyte populations are shifted to the DN4 stage (MGI Ref ID J:139069)
      • decreased B cell proliferation (MGI Ref ID J:149767)
      • decreased B cell proliferation (MGI Ref ID J:139069)
        • mutant mice exhibit impaired B cell proliferation after immunization with ovalbumin in Freund's complete adjuvant
      • decreased NK T cell number (MGI Ref ID J:149767)
      • decreased NK T cell number (MGI Ref ID J:139069)
      • decreased NK cell number (MGI Ref IDs J:139069, J:149767)
      • decreased gamma-delta T cell number (MGI Ref IDs J:139069, J:149767)
      • decreased immunoglobulin level (MGI Ref ID J:139069)
        • reduced basal serum immunoglobulin levels (IgM, IgG1, IgG2a, IgG2b, IgG3)
        • mutant mice fail to mount antigen-specific IgM and IgG responses after immunization with ovalbumin in Freund's complete adjuvant
        • decreased IgG1 level (MGI Ref ID J:149767)
          • decreases are greater than 1 log unit
        • decreased IgG1 level (MGI Ref ID J:139069)
        • decreased IgG2a level (MGI Ref IDs J:139069, J:149767)
          • (MGI Ref ID J:139069)
          • decreases are greater than 1 log unit (MGI Ref ID J:149767)
        • decreased IgG2b level (MGI Ref ID J:149767)
          • decreases are greater than 1 log unit
        • decreased IgG2b level (MGI Ref ID J:139069)
        • decreased IgG2c level (MGI Ref ID J:149767)
        • decreased IgG3 level (MGI Ref IDs J:139069, J:149767)
          • (MGI Ref ID J:139069)
          • decreases are greater than 1 log unit (MGI Ref ID J:149767)
        • decreased IgM level (MGI Ref IDs J:139069, J:149767)
          • (MGI Ref ID J:139069)
          • decreases are greater than 2 log units (MGI Ref ID J:149767)
      • decreased mature B cell number (MGI Ref ID J:149767)
        • decreased B-1 B cell number (MGI Ref ID J:139069)
          • peritoneal B1 cell numbers are reduced
        • decreased B-1 B cell number (MGI Ref ID J:149767)
      • decreased mature B cell number (MGI Ref ID J:139069)
        • decreased B-1 B cell number (MGI Ref ID J:139069)
          • peritoneal B1 cell numbers are reduced
        • decreased B-1 B cell number (MGI Ref ID J:149767)
      • decreased memory T cell number (MGI Ref IDs J:139069, J:149767)
        • (MGI Ref ID J:149767)
        • the numbers and proportions of memory CD4+ T cells are reduced (MGI Ref ID J:139069)
      • decreased regulatory T cell number (MGI Ref ID J:149767)
        • regulatory T cells are absent in the thymus and have a ten-fold reduction in the periphery
        • regulatory T cells in the periphery greatly expand in response to MCMV infection
      • dermatitis (MGI Ref ID J:149767)
        • some mice develop severe dermatitis with age
      • dermatitis (MGI Ref ID J:139069)
        • at 4-5 months of age, mutant mice have ~50% incidence of severe dermatitis
  • hematopoietic system phenotype
    • abnormal CD4-positive, CD25-positive, alpha-beta regulatory T cell morphology (MGI Ref ID J:149767)
      • regulatory T cells fail to develop when mutant bone marrow is transferred to wild-type mice suggesting defect is intrinsic to hematopoietic pre-cursors
      • in vitro, less activated CD4+ T cells express the regulatory marker FoxP3
    • abnormal T cell activation (MGI Ref ID J:139069)
      • in response to treatment with TCR-crosslinking antibodies (alpha-CD3/28), mutant T cells fail to upregulate CD25 (IL-2Ralpha chain), indicating impairment of TCR-mediated T cell activation
      • decreased T cell proliferation (MGI Ref IDs J:139069, J:149767)
        • (MGI Ref ID J:149767)
        • in response to treatment with TCR-crosslinking antibodies (alpha-CD3/28), mutant T cells fail to proliferate, indicating impairment of the TCR-mediated T cell proliferation response; the proliferation defect can be partially rescued by IL-2 treatment of mutant T cells (MGI Ref ID J:139069)
        • in vitro-expanded CD8+ T cells isolated from mutant mice a week after their immunization with irradiated ovalbumin (OVA) expressing cells fail to undergo secondary expansion upon restimulation (MGI Ref ID J:139069)
    • abnormal double-negative T cell morphology (MGI Ref IDs J:139069, J:149767)
      • (MGI Ref ID J:149767)
      • the double-negative thymocyte populations are shifted to the DN4 stage (MGI Ref ID J:139069)
    • decreased B cell proliferation (MGI Ref ID J:139069)
      • mutant mice exhibit impaired B cell proliferation after immunization with ovalbumin in Freund's complete adjuvant
    • decreased B cell proliferation (MGI Ref ID J:149767)
    • decreased NK T cell number (MGI Ref ID J:149767)
    • decreased NK T cell number (MGI Ref ID J:139069)
    • decreased NK cell number (MGI Ref IDs J:139069, J:149767)
    • decreased gamma-delta T cell number (MGI Ref IDs J:139069, J:149767)
    • decreased mature B cell number (MGI Ref ID J:149767)
      • decreased B-1 B cell number (MGI Ref ID J:139069)
        • peritoneal B1 cell numbers are reduced
      • decreased B-1 B cell number (MGI Ref ID J:149767)
    • decreased mature B cell number (MGI Ref ID J:139069)
      • decreased B-1 B cell number (MGI Ref ID J:139069)
        • peritoneal B1 cell numbers are reduced
      • decreased B-1 B cell number (MGI Ref ID J:149767)
    • decreased memory T cell number (MGI Ref IDs J:139069, J:149767)
      • (MGI Ref ID J:149767)
      • the numbers and proportions of memory CD4+ T cells are reduced (MGI Ref ID J:139069)
    • decreased regulatory T cell number (MGI Ref ID J:149767)
      • regulatory T cells are absent in the thymus and have a ten-fold reduction in the periphery
      • regulatory T cells in the periphery greatly expand in response to MCMV infection
  • integument phenotype
    • dermatitis (MGI Ref ID J:139069)
      • at 4-5 months of age, mutant mice have ~50% incidence of severe dermatitis
    • dermatitis (MGI Ref ID J:149767)
      • some mice develop severe dermatitis with age

Strain of Origin: C57BL/6J

Strain genetic background: C57BL/6J

Strain Development: The founder homozygous ENU-induced mutant was backcrossed to C57BL/6J. Heterozygote progeny were mated to the original mutant and homozygote progeny from this cross have subsequently been intercrossed to maintain the stock.

Suggested Control Mice: Wild-type littermates

Research Applications

  • Cell Biology
  • Developmental Biology
  • Diabetes/Obesity
  • Immunology and Inflammation
  • Virology

Strain Origin

Donor: Bruce Beutler, M.D., The Scripps Research Institute

Primary Reference:

  • Barnes MJ; Krebs P; Harris N; Eidenschenk C; Gonzalez-Quintial R; Arnold CN; Crozat K; Sovath S; Moresco EM; Theofilopoulos AN; Beutler B; Hoebe K, Commitment to the regulatory T cell lineage requires CARMA1 in the thymus but not in the periphery., PLoS Biol 2009 Mar 3;7(3):e51 (Medline PMID: 19260764)
  • For additional information see: Mutagenetix, a catalog of mutations identified in the Beutler Laboratory at The Scripps Research Institute.

Colony and Husbandry Information

Special Considerations

Donor notes homozygotes are susceptible to infection and dermatitis.

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@ucdavis.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
030114-UCD-RESUSLitter recovered from cryo-archive
$2,022.00
Non-Profit
Litter Recovered litter1; additional fees for any special requests.
030114-UCD-SPERMCryo-preserved spermatozoa
$437.00
Non-Profit
Aliquot Approximate quantity.2
030114-UCD-EMBRYOCryo-preserved embryos
$1,038.00
Non-Profit
Aliquot Approximate quantity3: 20-40 embryos / aliquot

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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