Strain Name:

B6;129S7-Nbntm1Jpt/J

Stock Number:

024335

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Availability:

Cryopreserved - Ready for recovery

Nbs1ΔB mice produce a truncated NBN protein lacking the BRCT domain. They may be useful when studying human chromosome instability syndromes such as Nijmegen Breakage Syndrome and 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

Former Names B6.129S7-Nbntm1Jpt/J    (Changed: 19-JUN-14 )
Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Mating SystemHeterozygote x Heterozygote         (Female x Male)   07-APR-14
Specieslaboratory mouse
 
Donating Investigator John Petrini,   Memorial Sloan-Kettering Cancer Center

Description
Nbs1ΔB mice have a floxed neo cassette replacing exons 4-5 of the nibrin (Nbn1) gene. NBN is a component of a trimeric protein complex also containing Mre11 and Rad50 which is involved in DNA double-strand break repair, cell cycle checkpoint activation, telomere maintenance, and meiotic recombination. Many Nbn mutations result in the production of a truncated protein missing regions required for effectively responding to DNA damage, resulting in a buildup of DNA strand breaks leading to radiation exposure sensitivity. Mutations in NBN have been found in patients with Nijmegen Breakage Syndrome (NBS), which is characterized by short stature, microcephaly, distinctive facial features, recurrent respiratory tract infections, an increased risk of cancer, and intellectual disability. Exons 4-5 encode the BRCT domain of NBN, removal of which causes a truncated 80 kDa isoform which is still capable of binding MRE11. Homozygous Nbs1Ddelta;B mice are viable and fertile. They are sensitive to gamma-irradiation and are prone to tumor development. Mouse embryonic fibroblasts (MEFs) from these mice exhibit defective cell cycle checkpoints after radiation.

Development
A targeting vector was designed to replace exons 4-5, encoding the BRCT domain, of the nibrin (Nbn1) gene with a loxP-flanked neomycin resistance (neo) in reverse orientation to the gene. The construct was electroporated into 129S7/SvEvBrd-Hprtb-m2-derived AB2.2 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric males were bred to C57BL/6 females. These mice were backcrossed at least 5 generations to C57BL/6 mice (see SNP note below). Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. Four of the 27 markers throughout the genome were segregating suggesting an incomplete backcross. Also, 2 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
Nijmegen Breakage Syndrome
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Aplastic Anemia   (NBN)
Leukemia, Acute Lymphoblastic; ALL   (NBN)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

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

Nbntm1Jpt/Nbntm1Jpt

        involves: 129S7/SvEvBrd
  • cellular phenotype
  • *normal* cellular phenotype
    • mice exhibit normal ionizing radiation-induced apoptosis in the developing nervous system and cultured thymocytes   (MGI Ref ID J:144172)
    • abnormal cell cycle checkpoint function
      • MEFs exhibit defective intra S phase and G2/M checkpoints after ionizing radiation treatment   (MGI Ref ID J:75956)
    • chromosome breakage
      • significantly higher levels of chromosomal aberrations following ionizing radiation treatment than wild-type, exhibiting increases in both deletion and exchange type aberrations   (MGI Ref ID J:75956)
    • increased cellular sensitivity to gamma-irradiation
      • MEFs exhibit pronounced sensitivity to ionizing radiation   (MGI Ref ID J:75956)
  • immune system phenotype
  • *normal* immune system phenotype
    • immunoglobulin isotype profiles are indistinguishable from controls and splenic B and thymic T cell propulations vary by less than 25% from wild-type   (MGI Ref ID J:75956)
  • reproductive system phenotype
  • *normal* reproductive system phenotype
    • male and females are fertile and exhibit no abnormalities in ovaries or testes   (MGI Ref ID J:75956)
  • tumorigenesis
  • *normal* tumorigenesis
    • homozygotes are not markedly prone to malignancy   (MGI Ref ID J:75956)
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 Nbntm1Jpt
Allele Name targeted mutation 1, John H J Petrini
Allele Type Targeted (Null/Knockout)
Common Name(s) Nbs1deltaB;
Strain of Origin129S7/SvEvBrd-Hprt
Gene Symbol and Name Nbn, nibrin
Chromosome 4
Gene Common Name(s) AT-V1; AT-V2; ATV; NBS; NBS1; P95;
Molecular Note Exons 4 and 5 were replaced with a floxed PGK-neo cassette via homologous recombination resulting in the deletion of the BRCT domain. An 80 kDa protein was expressed from the mutant allele as a result of a start codon originating in the PGK-neo cassette and splicing from intron 5 to exon 6. The mutant protein lacks the FHA and BRCT domains and retains Mre11a-binding activity. [MGI Ref ID J:75956]

Genotyping

Genotyping Information

Genotyping Protocols

Nbntm1Jpt-Alternate1, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Williams BR; Mirzoeva OK; Morgan WF; Lin J; Dunnick W; Petrini JH. 2002. A murine model of nijmegen breakage syndrome. Curr Biol 12(8):648-53. [PubMed: 11967151]  [MGI Ref ID J:75956]

Additional References

Nbntm1Jpt related

Brugmans L; Kanaar R; Essers J. 2007. Analysis of DNA double-strand break repair pathways in mice. Mutat Res 614(1-2):95-108. [PubMed: 16797606]  [MGI Ref ID J:118077]

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]

Daniel JA; Pellegrini M; Lee BS; Guo Z; Filsuf D; Belkina NV; You Z; Paull TT; Sleckman BP; Feigenbaum L; Nussenzweig A. 2012. Loss of ATM kinase activity leads to embryonic lethality in mice. J Cell Biol 198(3):295-304. [PubMed: 22869595]  [MGI Ref ID J:191289]

Foster SS; De S; Johnson LK; Petrini JH; Stracker TH. 2012. Cell cycle- and DNA repair pathway-specific effects of apoptosis on tumor suppression. Proc Natl Acad Sci U S A 109(25):9953-8. [PubMed: 22670056]  [MGI Ref ID J:185501]

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]

Halberg RB; Waggoner J; Rasmussen K; White A; Clipson L; Prunuske AJ; Bacher JW; Sullivan R; Washington MK; Pitot HC; Petrini JH; Albertson DG; Dove WF. 2009. Long-lived Min mice develop advanced intestinal cancers through a genetically conservative pathway. Cancer Res 69(14):5768-75. [PubMed: 19584276]  [MGI Ref ID J:150641]

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]

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; Morales M; Couto SS; Hussein H; Petrini JH. 2007. The carboxy terminus of NBS1 is required for induction of apoptosis by the MRE11 complex. Nature 447(7141):218-21. [PubMed: 17429352]  [MGI Ref ID J:129762]

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]

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]

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, homozygotes may be bred together.
Mating SystemHeterozygote x Heterozygote         (Female x Male)   07-APR-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 willfulfill 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 willfulfill 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
   Wild-type from the colony
   000664 C57BL/6J (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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