Strain Name:

B6;129P2-Terf2tm1Tdl/J

Stock Number:

006568

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Cryopreserved - Ready for recovery

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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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Specieslaboratory mouse
GenerationN?+F1pN1
Generation Definitions
 
Donating Investigator Titia de Lange,   The Rockefeller University

Description
These mice possess loxP sites on either side of exons 1 and 2 of the targeted gene. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. When used in conjunction with a Cre recombinase-expressing strain, this strain is useful in generating tissue-specific mutants of the floxed allele that can result in acute telomere dysfunction.

For example, when crossed to a strain expressing interferon inducible Cre recombinase (see Stock No. 003556), this mutant mouse strain may be useful in studies of telomere damage response.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes under the control of the phosphoglyceryl kinase gene promoter was utilized in the construction of this mutant. A loxP site was inserted upstream of exon 1. Another loxP site was inserted downstream of exon 2. This construct was electroporated into 129P2/OlaHsd derived E14 embryonic stem (ES) cells which were transiently transfected with a Cre recombinase vector to remove the selection cassette. Correctly targeted ES cells were injected into recipient blastocysts. The Donating Investigator maintained the strain on a mixed B6;129P2 background.

Control Information

  Control
   100492 B6129PF1/J (approximate)
 
  Considerations for Choosing Controls

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype relates to a compound genotype created using this strain.
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Terf2tm1Tdl/Terf2tm1.1Tdl Tg(Mx1-cre)1Cgn/0

        involves: 129/Sv * 129P2/OlaHsd * C57BL/6 * CBA   (conditional)
  • cellular phenotype
  • abnormal chromosome morphology
    • following pI-pC injection to induce cre expression, telomeres undergo end-to-end fusions in quiescent hepatocytes, indicating telomere deprotection, however, hepatocytes are resistant to this damage and are functional in the presence of chromosome end fusions as indicated by normal liver function   (MGI Ref ID J:112957)
    • the telomere fusions seen in mutants do not impair liver regeneration after partial hepatectomy as regeneration occurs without cell division involving endoreduplication and cell growth, circumventing the chromosome segregation problems associated with telomere fusions   (MGI Ref ID J:112957)
  • liver/biliary system phenotype
  • abnormal hepatocyte morphology
    • following pI-pC injection to induce cre expression, telomeres undergo end-to-end fusions in quiescent hepatocytes, indicating telomere deprotection, however, hepatocytes are resistant to this damage and are functional in the presence of chromosome end fusions as indicated by normal liver function   (MGI Ref ID J:112957)
View Research Applications

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

Research Tools
Cre-lox System
      loxP-flanked Sequences

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Terf2tm1Tdl
Allele Name targeted mutation 1, Titia de Lange
Allele Type Targeted (Conditional ready (e.g. floxed), No functional change)
Common Name(s) TRF2f;
Mutation Made By Titia de Lange,   The Rockefeller University
Strain of Origin129P2/OlaHsd
ES Cell Line NameE14
ES Cell Line Strain129P2/OlaHsd
Gene Symbol and Name Terf2, telomeric repeat binding factor 2
Chromosome 8
Gene Common Name(s) TRBF2; TRF2;
General Note After transient Cre expression, homozygous MEFs display a senescence-like arrest of cell proliferation (J:105516).
Molecular Note LoxP sites were inserted to flank exons 1 and 2. [MGI Ref ID J:105516]

Genotyping

Genotyping Information

Genotyping Protocols

Terf2tm1Tdl, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Celli GB; de Lange T. 2005. DNA processing is not required for ATM-mediated telomere damage response after TRF2 deletion. Nat Cell Biol 7(7):712-8. [PubMed: 15968270]  [MGI Ref ID J:105516]

Additional References

Terf2tm1Tdl related

Bekes M; Okamoto K; Crist SB; Jones MJ; Chapman JR; Brasher BB; Melandri FD; Ueberheide BM; Denchi EL; Huang TT. 2013. DUB-resistant ubiquitin to survey ubiquitination switches in mammalian cells. Cell Rep 5(3):826-38. [PubMed: 24210823]  [MGI Ref ID J:205527]

Bojovic B; Ho HY; Wu J; Crowe DL. 2013. Stem cell expansion during carcinogenesis in stem cell-depleted conditional telomeric repeat factor 2 null mutant mice. Oncogene 32(43):5156-66. [PubMed: 23178498]  [MGI Ref ID J:203237]

Celli GB; Denchi EL; de Lange T. 2006. Ku70 stimulates fusion of dysfunctional telomeres yet protects chromosome ends from homologous recombination. Nat Cell Biol 8(8):885-90. [PubMed: 16845382]  [MGI Ref ID J:115641]

Dimitrova N; Chen YC; Spector DL; de Lange T. 2008. 53BP1 promotes non-homologous end joining of telomeres by increasing chromatin mobility. Nature 456(7221):524-8. [PubMed: 18931659]  [MGI Ref ID J:143563]

Konishi A; de Lange T. 2008. Cell cycle control of telomere protection and NHEJ revealed by a ts mutation in the DNA-binding domain of TRF2. Genes Dev 22(9):1221-30. [PubMed: 18451109]  [MGI Ref ID J:134654]

Lazzerini Denchi E; Celli G; de Lange T. 2006. Hepatocytes with extensive telomere deprotection and fusion remain viable and regenerate liver mass through endoreduplication. Genes Dev 20(19):2648-53. [PubMed: 17015429]  [MGI Ref ID J:112957]

Lottersberger F; Bothmer A; Robbiani DF; Nussenzweig MC; de Lange T. 2013. Role of 53BP1 oligomerization in regulating double-strand break repair. Proc Natl Acad Sci U S A 110(6):2146-51. [PubMed: 23345425]  [MGI Ref ID J:194338]

Martinez P; Ferrara-Romeo I; Flores JM; Blasco MA. 2014. Essential role for the TRF2 telomere protein in adult skin homeostasis. Aging Cell :. [PubMed: 24725274]  [MGI Ref ID J:210514]

Peuscher MH; Jacobs JJ. 2011. DNA-damage response and repair activities at uncapped telomeres depend on RNF8. Nat Cell Biol 13(9):1139-45. [PubMed: 21857671]  [MGI Ref ID J:176962]

Sfeir A; Kabir S; van Overbeek M; Celli GB; de Lange T. 2010. Loss of Rap1 induces telomere recombination in the absence of NHEJ or a DNA damage signal. Science 327(5973):1657-61. [PubMed: 20339076]  [MGI Ref ID J:158884]

Sfeir A; de Lange T. 2012. Removal of shelterin reveals the telomere end-protection problem. Science 336(6081):593-7. [PubMed: 22556254]  [MGI Ref ID J:184522]

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, these mice are bred as homozygotes.

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
   100492 B6129PF1/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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