Strain Name:

B6;129S7-Mre11atm1Jpt/J

Stock Number:

024172

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Availability:

Cryopreserved - Ready for recovery

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These Mre11ATLD1/ATLD1 mice contain a mutation in the Mre11 gene, similar to that found in humans with ataxia-telangiectasia like disorder.

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

Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Mating SystemHeterozygote x Heterozygote         (Female x Male)   22-JAN-14
Specieslaboratory mouse
 
Donating Investigator John Petrini,   Memorial Sloan-Kettering Cancer Center

Description
These Mre11ATLD1/ATLD1 mice contain an A to T point mutation at nucleotide 1894, corresponding to human codon 633, of the meiotic recombination 11 homolog A (Mre11) gene. MRE11 is a component of a trimeric protein complex also containing Nbs1 and Rad50 which is involved in DNA double-strand break repair, cell cycle checkpoint activation, telomere maintenance, and meiotic recombination. This mutation introduces a premature stop codon, resulting in the truncation of 75 amino acids which produces a hypomorphic protein. This mutation is commonly found in human ataxia-telangiectasia like disorder (A-TLD) and Nijmegen Breakage Syndrome (NBS). A-TLD is characterized by defects in movement, coordination, and immune responses due to chromosomal instability. NBS is characterized by short stature, microcephaly, distinctive facial features, recurrent respiratory tract infections, an increased risk of cancer, and intellectual disability. Homozygous Mre11ATLD1/ATLD1 females have severely reduced fertility, with decreased embryonic viability due to genome instability and cell cycle checkpoint defects. Homozygous males are viable and fertile. These mice, and cells derived from these mice, exhibit DNA double strand break repair defects, cell-cycle checkpoint defects, and chromosomal instability. These mice are not prone to malignancy including lymphomagenesis.

Development
A targeting construct was designed to introduce an A to T point mutation at nucleotide 1894, corresponding to human codon 633, resulting in a premature STOP codon in the meiotic recombination 11 homolog A (Mre11) gene, commonly found in human ataxia-telangiectasia like disorder (A-TLD). A neomycin resistance cassette was placed downstream of the mutation. This targeting construct was electroporated into 129S7/SvEvBrd-Hprtb-m2-derived AB2.2 embryonic stem (ES) cells and correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric males were bred to C57BL/6 females. These Mre11ATLD1/ATLD1 mice were maintained on a mixed background. Upon arrival at The Jackson Laboratory, mutant mice were bred to C57BL/6J mice (Stock No. 000664) for at least one generation to establish the colony.

Control Information

  Control
   101045 B6129SF2/J (approximate)
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Mre11a
018445   B6.129-Mre11atm1.1Rchd/J
View Strains carrying other alleles of Mre11a     (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.
Ataxia-Telangiectasia-Like Disorder 1; ATLD1   (MRE11A)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Mre11atm1Jpt/Mre11atm1Jpt

        involves: 129S7/SvEvBrd * C57BL/6
  • cellular phenotype
  • abnormal cell cycle checkpoint function
    • MEFs exhibit defects in G1/S, intra-S-phase, and G2/M checkpoints after ionizing radiation induced DNA damage   (MGI Ref ID J:103922)
    • checkpoint defects; MEFs fail to arrest or suffer attrition either in S phase or at the G2/M border   (MGI Ref ID J:87088)
  • chromosomal instability
    • passage 7 MEFs show chromosomal instability; 43% vs. 19% of wild-type metaphases contain at least 1 aberration and the number of aberrations per metaphase is increased   (MGI Ref ID J:87088)
    • 33% of early passage MEFs (p3) and 65% of late passage (greater than 5) MEFs show aberrant metaphases   (MGI Ref ID J:87088)
    • translocasions and fusions are seen in 5 of 32 early and 7 of 27 late passage MEFs   (MGI Ref ID J:87088)
    • 18% of metaphases in splenocyte cultures exhibit aberrations   (MGI Ref ID J:87088)
    • chromosome breakage   (MGI Ref ID J:103922)
      • induced chromosome breakage
        • MEFs are hypersensitive to irradiation-induced chromosome breakage   (MGI Ref ID J:87088)
  • increased cellular sensitivity to ionizing radiation
    • MEFs exhibit increased sensitivity to ionizing radiation   (MGI Ref ID J:103922)
    • mouse embryonic fibroblasts (MEFs) are sensitive to ionizing radiation   (MGI Ref ID J:87088)
  • reproductive system phenotype
  • reduced female fertility   (MGI Ref ID J:87088)
  • other phenotype
  • maternal effect
    • embryonic viability is drastically reduced in homozygous mothers but not in heterozygous intercrosses, indicating a maternal effect on viability   (MGI Ref ID J:87088)
  • tumorigenesis
  • *normal* tumorigenesis
    • inspite of cell cycle checkpoint failure and chromosomal instability, mice are not prone to malignancy including lymphomagenesis   (MGI Ref ID J:87088)

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Mre11atm1Jpt/Mre11atm1Jpt

        involves: 129S7/SvEvBrd
  • cellular phenotype
  • decreased cellular sensitivity to ionizing radiation
    • at E13.5, E15.5, and P5, mice exhibit resistance to ionizing radiation-induced apoptosis in the retina and dentate gyrus compared to wild-type mice   (MGI Ref ID J:144172)
    • ionizing radiation-induced apoptosis in the thymus is reduced compared to in wild-type mice   (MGI Ref ID J:144172)
    • however, ionizing radiation-induced apoptosis in the proliferating embryonic ventricular zone is normal   (MGI Ref ID J:144172)
View Research Applications

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

Cancer Research
Other
      DNA Repair

Cell Biology Research
Cell Cycle Regulation
DNA Damage Response

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Mre11atm1Jpt
Allele Name targeted mutation 1, John H J Petrini
Allele Type Targeted
Common Name(s) Mre11ATLD1;
Strain of Origin129S7/SvEvBrd-Hprt
Gene Symbol and Name Mre11a, meiotic recombination 11 homolog A (S. cerevisiae)
Chromosome 9
Gene Common Name(s) ATLD; HNGS1; MRE11; MRE11B;
Molecular Note An A-to-T transversion point mutation was engineered at nucleotide 1894 of the coding sequence to recapitulate a nonsense mutation identified in human patients (codon 633). This mutation results in the truncation of 75 amino acids. [MGI Ref ID J:87088]

Genotyping

Genotyping Information

Genotyping Protocols

Mre11atm1Jpt-Alternate2, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Theunissen JW; Kaplan MI; Hunt PA; Williams BR; Ferguson DO; Alt FW; Petrini JH. 2003. Checkpoint failure and chromosomal instability without lymphomagenesis in Mre11(ATLD1/ATLD1) mice. Mol Cell 12(6):1511-23. [PubMed: 14690604]  [MGI Ref ID J:87088]

Additional References

Mre11atm1Jpt related

Attwooll CL; Akpinar M; Petrini JH. 2009. The mre11 complex and the response to dysfunctional telomeres. Mol Cell Biol 29(20):5540-51. [PubMed: 19667076]  [MGI Ref ID J:153902]

Cherry SM; Adelman CA; Theunissen JW; Hassold TJ; Hunt PA; Petrini JH. 2007. The Mre11 complex influences DNA repair, synapsis, and crossing over in murine meiosis. Curr Biol 17(4):373-8. [PubMed: 17291760]  [MGI Ref ID J:120745]

Gupta GP; Vanness K; Barlas A; Manova-Todorova KO; Wen YH; Petrini JH. 2013. The Mre11 complex suppresses oncogene-driven breast tumorigenesis and metastasis. Mol Cell 52(3):353-65. [PubMed: 24120666]  [MGI Ref ID J:205983]

Helmink BA; Bredemeyer AL; Lee BS; Huang CY; Sharma GG; Walker LM; Bednarski JJ; Lee WL; Pandita TK; Bassing CH; Sleckman BP. 2009. MRN complex function in the repair of chromosomal Rag-mediated DNA double-strand breaks. J Exp Med 206(3):669-79. [PubMed: 19221393]  [MGI Ref ID J:146799]

Morales M; Liu Y; Laiakis EC; Morgan WF; Nimer SD; Petrini JH. 2008. DNA damage signaling in hematopoietic cells: a role for Mre11 complex repair of topoisomerase lesions. Cancer Res 68(7):2186-93. [PubMed: 18381424]  [MGI Ref ID J:133303]

Morales M; Theunissen JW; Kim CF; Kitagawa R; Kastan MB; Petrini JH. 2005. The Rad50S allele promotes ATM-dependent DNA damage responses and suppresses ATM deficiency: implications for the Mre11 complex as a DNA damage sensor. Genes Dev 19(24):3043-54. [PubMed: 16357220]  [MGI Ref ID J:103922]

Rotolo JA; Mesicek J; Maj J; Truman JP; Haimovitz-Friedman A; Kolesnick R; Fuks Z. 2010. Regulation of ceramide synthase-mediated crypt epithelium apoptosis by DNA damage repair enzymes. Cancer Res 70(3):957-67. [PubMed: 20086180]  [MGI Ref ID J:156862]

Shull ER; Lee Y; Nakane H; Stracker TH; Zhao J; Russell HR; Petrini JH; McKinnon PJ. 2009. Differential DNA damage signaling accounts for distinct neural apoptotic responses in ATLD and NBS. Genes Dev 23(2):171-80. [PubMed: 19171781]  [MGI Ref ID J:144172]

Stracker TH; Couto SS; Cordon-Cardo C; Matos T; Petrini JH. 2008. Chk2 suppresses the oncogenic potential of DNA replication-associated DNA damage. Mol Cell 31(1):21-32. [PubMed: 18614044]  [MGI Ref ID J:138550]

Stracker TH; Williams BR; Deriano L; Theunissen JW; Adelman CA; Roth DB; Petrini JH. 2009. Artemis and nonhomologous end joining-independent influence of DNA-dependent protein kinase catalytic subunit on chromosome stability. Mol Cell Biol 29(2):503-14. [PubMed: 19015239]  [MGI Ref ID J:144749]

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 & HusbandryWhen maintaining a live colony, heterozygous females may be bred to homozygous males. Homozygous females are extremely subfertile.
Mating SystemHeterozygote x Heterozygote         (Female x Male)   22-JAN-14

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* $2140.00
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 will fulfill 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* $2782.00
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 will fulfill 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
   101045 B6129SF2/J (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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.
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