Strain Detail Sheet

Strain Name:
B6;129S6-Xrcc6tm1Fwa/Mmucd
Stock Number:
014116-UCD
Citation ID:
RRID:MMRRC_014116-UCD
Other Names:
Ku70 -/- or Ku70 null, B6;129S6-Xrcc6tm1Fwa/Mmcd

Strain Information

Gene Details

Xrcc6tm1Fwa
Name: X-ray repair complementing defective repair in Chinese hamster cells 6; targeted mutation 1, Frederick W Alt
Synonyms: Ku70DKO, Ku70-
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 15
Alteration at locus: Knockout
Xrcc6
Name: X-ray repair complementing defective repair in Chinese hamster cells 6
Synonyms: Ku p70, Ku70, G22p1
Type: Gene
Species: Mouse
Chromosome: 15
Alteration at locus: Knockout
NCBI: 14375
HGNC: HGNC:4055
Homologene: 37483
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Genetic Alterations
A Ku70 targeting construct was used to target the Ku70 gene in TC1 ES cells. Homozygous replacement of exons 4 and 5 of the Ku70 gene with a neomycin-resistance gene disrupted Ku70 expression. Two independent ES clones carrying the desired mutation were identified by Southern blot analysis and were injected into C57BL/6J blastocysts by standard methods. Both clones gave a high percentage of chimeras, and each transmitted the mutation efficiently into the mouse germline, resulting in a mixed background (129/Sv x C57BL/6J).
Genotype Determination

Genotyping Protocol

ES Cell Line
TC1/TC-1 derived from 129S6/SvEvTac

Strain Description

Phenotype
Homozygous: Ku is a heterodimer of 70 kDa (Ku70) and 80 kDa (Ku80) subunits that binds to DNA double-strand breaks (DSBs) without DNA sequence specificity. The DNA end-bound Ku heterodimer can associate with the catalytic subunit of the DNA-dependent protein kinase (DNA-PK), DNA-PKcs, and thereby activate its kinase activity, suggesting that one major role for Ku is to function as the DNA-binding subunit of this enzyme. To elucidate further the function of Ku and DNA-PK, donor generated mice homozygous for an inactivating mutation of the Ku70 gene.

Donor's Ku70-deficient mice were about 50% the size of control littermates, and their fibroblasts were ionizing sensitive and displayed premature senescence associated with the accumulation of nondividing cells. Ku70-deficient mice lacked mature B cells or serum immunoglobulin, but unexpectedly, reproducibly developed small populations of thymic and peripheral α/β T lineage cells and had a significant incidence of thymic lymphomas. In association with B and T cell developmental defects, Ku70-deficient cells were severely impaired for joining of V(D)J coding and recombination signal sequences.

In summary, the phenotype includes:
  • Ku70 deficiency leads to growth retardation
  • Reduced Ku80 protein levels in Ku70-deficient mice
  • Early senescence of Ku70-deficient cells
  • Leaky” T Cell Development
  • Increased incidence of thymic tumors in Ku70-deficient mice
  • Early arrest of B cell development in Ku70-deficient mice
  • Ku70-/- cells display inefficient V(D)J recombination in vitro
  • Ku70-deficient mice have abnormal TCR V(D)J recombination in vivo

    • Heterozygous: Mice heterozygous for the Ku70 mutation (Ku70+/-) were indistinguishable from the wild type (Ku70+/+) mice in all examined aspects. Ku70-/- females were unable to nurse their newborns, and pups required a foster mother for survival.
    Mammalian Phenotype Terms
    Allelic Composition: Xrcc6tm1Fwa/Xrcc6tm1Fwa (Genetic Background: involves: 129S6/SvEvTac )
    Allelic Composition: Xrcc6tm1Fwa/Xrcc6tm1Fwa (Genetic Background: involves: 129S6/SvEvTac * C57BL/6J )
    MeSH Terms
    • Animals
    • Antigens, Nuclear
    • B-Lymphocytes/cytology
    • Cell Cycle
    • Cells, Cultured
    • Cellular Senescence
    • DNA Damage
    • DNA Helicases
    • DNA Repair
    • DNA-Activated Protein Kinase
    • DNA-Binding Proteins/physiology
    • Fetal Growth Retardation/genetics
    • Fibroblasts/cytology
    • Gene Rearrangement, B-Lymphocyte
    • Gene Rearrangement, T-Lymphocyte
    • Ku Autoantigen
    • Mice
    • Mice, Knockout
    • Mice, SCID/genetics
    • Nuclear Proteins/physiology
    • Protein-Serine-Threonine Kinases/deficiency
    • T-Lymphocytes/cytology
    • Thymus Neoplasms/genetics
    Strain Development
    Two independently targeted ES clones were used to generate chimeric mice, which transmitted the mutation efficiently into the mouse germline. The Ku70+/- mice were interbred and found to produce homozygous Ku70 mutant (Ku70-/-) progeny at the expected Mendelian frequency. All mice were housed with littermates of the same sex in a pathogen-free facility.
    Suggested Control Mice

    Wildtype littermates

    MMRRC Genetic QC

    MMRRC Genetic QC Summary
    The MMRRC Centers have developed a genetic QC pipeline using MiniMUGA array genotyping to provide additional information on strain backgrounds for MMRRC congenic and inbred strains. For more information on when data may be available, or to request genotyping for a strain of interest, please contact mmrrc@ucdavis.edu. Older strains may not have this information.

    Research Applications

    • Developmental Biology
    • Immunology and Inflammation
    • Models for Human Disease
    • Neurobiology

    Strain Origin

    Donor
    Yansong Gu, Ph.D., University of Washington
    Primary Reference
    Gu Y, Seidl KJ, Rathbun GA, Zhu C, Manis JP, van der Stoep N, Davidson L, Cheng HL, Sekiguchi JM, Frank K, Stanhope-Baker P, Schlissel MS, Roth DB, Alt FW. Growth retardation and leaky SCID phenotype of Ku70-deficient mice. Immunity. 1997 Nov;7(5):653-65. (Medline PMID: 9390689)

    Colony and Husbandry Information

    Health Status Report

    Colony Surveillance Program and Current Health Reports

    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.

    Cryopreserved material may be available upon request, please inquire to mmrrc@ucdavis.edu for more information.

    Conditions of Distribution

    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.

    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 $)
    *Shipping & Handling not included*    		 Units Notes
    014116-UCD-EMBRYO Cryo-preserved embryos $1,038.00 / $1,545.65
    Non-Profit / For-Profit    		 Aliquot Approximate quantity2 : 20-40 embryos / aliquot
    014116-UCD-SPERM Cryo-preserved spermatozoa $546.25 / $869.88
    Non-Profit / For-Profit    		 Aliquot Approximate quantity3
    014116-UCD-RESUS Litter recovered from cryo-archive $4,044.00 / $7,650.23
    Non-Profit / For-Profit    		 Litter Recovered litter4; additional fees for any special requests.

    1 The distribution fee covers the expense of rederiving mice from a live mouse; 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 contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

    3 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.

    4 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.

    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.