Strain Detail Sheet

Strain Name    :

C57BL/6J-Ikbkgm1Btlr/Mmucd

Stock Number :

030659-UCD

Other Names   :

panr2, C57BL/6J-Ikbkgm1Btlr/Mmcd

Gene Information

Gene Details [Including genotyping protocols]

(provided by MGI)
Allele Symbol: Ikbkgm1Btlr
Name: mutation 1, Bruce Beutler
Alteration at locus: Chemically Induced
Gene Symbol: Ikbkg
Name: inhibitor of kappaB kinase gamma
Chromosome: X
Alteration at locus: Chemically Induced

Genetic Alterations:
The Ikbkg gene on the X chromosome of panr2 mice was sequenced, and a T to C transition was identified in exon 4 (of 10 total exons) at position 473 (using variant 1, Genbank: NM_178590). The mutation results in a leucine to proline change at amino acid 153 of the IKK-Υ or NEMO protein.

Genotype Determination:

ES Cell Line: Not Applicable

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

Phenotype

Homozygous and Hemizygous phenotype: The panr2 ("pan- resistance") phenotype was detected in a screen of ENU-induced mutant mice for altered responses to Toll-like receptor (TLR) ligands (TLR Signaling Screen). Peritoneal macrophages from panr2 mice exhibit low tumor necrosis factor (TNF)-α production to all TLR ligands except the TLR4 ligand, lipopolysaccharide (LPS). Only a subtle reduction in TNF-α production is seen in these macrophages when stimulated with LPS. In response to the TLR3 ligand poly I:C (a dsRNA mimetic) and dsDNA, panr2 macrophages display normal type 1 interferon (IFN) production. Panr2 mice display normal natural killer (NK) cell and cytotoxic T cell (CTL) function (In vivo NK cell and CD8+ T cell cytotoxicity screen).

Although the TLR sensing defect remains as reported and hemizygous males remain azoospermatic, this mutation is no longer associated with male lethality.


Mammalian Phenotype Terms:(provided by MGI)      Extend all MPTs
      assigned by genotype
Ikbkgm1Btlr/Ikbkg+
        C57BL/6J-Ikbkg<m1Btlr>
  • reproductive system phenotype
    • reduced female fertility (MGI Ref ID J:139558)
      • female mice heterozygous for this mutation are poor breeders
Ikbkgm1Btlr/-
        C57BL/6J-Ikbkg<m1Btlr>
  • mortality/aging
    • mortality/aging (MGI Ref ID J:139558)
      • despite earlier reports that hemizygous males are born at a lower-than-expected frequency, larger numbers of births showed that hemizygotes are born at the expected Mendelian ratio; they survive for at least 4-6 weeks
  • reproductive system phenotype
  • immune system phenotype
    • immune system phenotype (MGI Ref ID J:139558)
      • type 1 interferon (IFN) production by macrophages from hemizygous mutant male mice in response to the toll-like receptor (TLR) 3 ligand poly I:C (a dsRNA mimetic) and to dsDNA is normal
      • mutant mice have normal CD8+ lymphocyte function
      • decreased regulatory T cell number (MGI Ref ID J:139558)
        • mutant mice have a two-fold reduction in peripheral CD4+CD25+ lymphocytes (regulatory T cells)
      • decreased tumor necrosis factor secretion (MGI Ref ID J:139558)
        • upon stimulation with the TLR4 ligand, lipopolysaccharide (LPS), peritoneal macrophages from hemizygous mutant male mice exhibit a s ubtly reduced TNF-alpha response compared to that of wild-type mice
        • mutant macrophages produce normal amounts of tumor necrosis factor (TNF) alpha in response to stimulation with all other toll-like receptor (TLR) ligands tested: the TLR3 ligand poly(I:C); the TLR1/2 ligand Pam3CSK4; the TLR7 ligand resiquimod; the TLR9 ligand CpG ODN; and the TLR6 ligands peptidoglycan and MALP-2
  • hematopoietic system phenotype
    • decreased regulatory T cell number (MGI Ref ID J:139558)
      • mutant mice have a two-fold reduction in peripheral CD4+CD25+ lymphocytes (regulatory T cells)

Strain of Origin: C57BL/6J

Strain genetic background: C57BL/6J

Strain Development: Original mutant was a C57BL/6J G3 ENU-induced mutant; all subsequent crosses to maintain strain were on C57BL/6J background only.

Suggested Control Mice: Wild-type littermates or C57BL/6J

Research Applications

  • Immunology and Inflammation
  • Models for Human Disease

Strain Origin

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

Primary Reference:

  • Siggs OM, Berger M, Krebs P, Arnold CN, Eidenschenk C, Huber C, Pirie E, Smart NG, Khovananth K, Xia Y, McInerney G, Karlsson Hedestam GB, Nemazee D, Beutler B. A mutation of Ikbkg causes immune deficiency without impairing degradation of IkappaB alpha. Proc Natl Acad Sci U S A 2010 Feb 16;107(7):3046-51 (Medline PMID: 20133626)
  • Siggs OM, Smart NG, Beutler B. Record for panr2MUTAGENETIX™, B. Beutler and colleagues, The Scripps Research Institute, La Jolla, CA.

Colony and Husbandry Information

Special Considerations

Donor recommends TMS antibiotic water. Hemizygous panr2 males are sterile and homozygous females do not breed. Therefore heterozygous females must be bred to wild-type males to maintain the stock. Heterozygous females are also poor breeders.

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.

Appearance

Coat color: Black

Other:

Breeding

MMRRC Breeding System: Random intra-strain mating

Breeding Scheme(s):

  • Heterozygous female x C57BL/6J male.

Generation:

Overall Breeding Performance: Fair

Reproductive Statistics

NOTE: "Hemizygote" as used here refers to males carrying a mutation on the X Chromosome or mice of either sex carrying an inserted transgene with no homologous allele on the other chromosome.

Viability and Fertility:FemaleMale
Homozygotes are viable: Yes Yes
Homozygotes are fertile: No No
Hetero/Hemizygotes are fertile: Yes No Heterozygous females are poor breeders, males are sterile

Age Reproductive Decline: Unknown Unknown

Average litter size:

Recommended wean age: 3 weeks

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.

Onco-Mouse Patents. Canada: CA1341442 expires Oct. 7, 2020. US patents: 5,925,803 expires July 20, 2016 5,807,571 expired Feb. 11, 2009 4,736,866 expired April 12, 2005

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
030659-UCD-RESUSLitter recovered from cryo-archive
$2,022.00
Non-Profit
Litter Recovered litter1; additional fees for any special requests.
030659-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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