Strain Name:

B6.129S4(Cg)-Trp53tm2.1Tyj/J

Stock Number:

008183

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Cryopreserved - Ready for recovery

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Mice carrying this Trp53 (p53) R172H point mutation mimic human Li-Fraumeni Syndrome, both genotypically and phenotypically. Heterozygotes develop a broad spectrum of tumors with a mean survival time of 16 months. Prominent tumor types include osteosarcomas (often metastatic), hemangiosarcomas, B-cell lymphomas and a variety of carcinomas. Homozygous mice also develop a broad spectrum of tumors, particularly T-cell lymphomas, hemangiosarcomas, soft-tissue sarcomas, osteosarcomas, primitive tumors (particularly male teratocarcinomas), and a variety of epithelial carcinomas.

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 Congenic; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
 
Donating InvestigatorDr. Tyler Jacks,   Massachusetts Institute of Technology

Description
Mice carrying this Trp53 (p53) R172H point mutation mimic human Li-Fraumeni Syndrome, both genotypically and phenotypically. Heterozygotes develop a broad spectrum of tumors with a mean survival time of 16 months. Prominent tumor types include osteosarcomas (often metastatic), hemangiosarcomas, B-cell lymphomas and a variety of carcinomas. Homozygous mice also develop a broad spectrum of tumors, particularly T-cell lymphomas, hemangiosarcomas, soft-tissue sarcomas, osteosarcomas, primitive tumors (particularly male teratocarcinomas), and a variety of epithelial carcinomas. Mutant protein is expressed at high levels in mouse embryonic fibroblasts, as determined by Western blotting.

Development
A targeting vector was designed to place a loxP-flanked stop cassette in intron 1 and an R172H missense mutation into exon 5. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Resultant mice were crossed with a protamine promoter-driven Cre strain on an undetermined background to remove the stop cassette. The strain was backcrossed to C57BL/6 approximately 5 times by the donating laboratory.

Related Strains

View Strains carrying other alleles of Trp53     (26 strains)

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).
Li-Fraumeni Syndrome 1; LFS1
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Adrenocortical Carcinoma, Hereditary; ADCC   (TP53)
Basal Cell Carcinoma, Susceptibility to, 7; BCC7   (TP53)
Breast Cancer   (TP53)
Colorectal Cancer; CRC   (TP53)
Glioma Susceptibility 1; GLM1   (TP53)
Hepatocellular Carcinoma   (TP53)
Nasopharyngeal Carcinoma   (TP53)
Osteogenic Sarcoma   (TP53)
Pancreatic Cancer   (TP53)
Papilloma of Choroid Plexus   (TP53)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

Trp53tm2.1Tyj/Trp53+

        involves: 129S4/SvJae
  • mortality/aging
  • premature death
    • mean life span is 15.2 months   (MGI Ref ID J:95316)
  • tumorigenesis
  • increased metastatic potential
    • tumors metastisize more frequently than those in Trp53tm1Tyj or Trp53tm3.1Tyj heterozygotes   (MGI Ref ID J:95316)
  • cellular phenotype
  • decreased cellular sensitivity to gamma-irradiation
    • resistance to gamma-irradiation induced apoptosis is increased compared to Trp53tm1Tyj heterozygotes   (MGI Ref ID J:95316)
  • increased cell proliferation
    • a larger fraction of MEFs are in S phase compared to Trp53tm1Tyj hterozygotes; however DNA damage-induced G1 arrest is intact   (MGI Ref ID J:95316)
  • skeleton phenotype
  • osteopetrosis
    • diffuse osteopetrosis is frequently observed with osteosarcomas   (MGI Ref ID J:95316)
View Research Applications

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

Cancer Research
Increased Tumor Incidence
      Lymphomas
      Lymphomas: B cell lymphomas
      Other Tissues/Organs
      Other Tissues/Organs: multiple
      Skin Cancers
Oncogenes

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Trp53tm2.1Tyj
Allele Name targeted mutation 2.1, Tyler Jacks
Allele Type Targeted (knock-in)
Common Name(s) TrpR172H; p53 R172H; p53R172H;
Mutation Made ByDr. Tyler Jacks,   Massachusetts Institute of Technology
Strain of Origin129S4/SvJae
ES Cell Line NameJ1
ES Cell Line Strain129S4/SvJae
Promoter Trp53, transformation related protein 53, mouse, laboratory
Molecular Note The loxP flanked stop cassette was removed from Trp53tm2Tyj via cre-mediated recombination, leaving an R172H missense mutation in exon 5. Quantitative real-time PCR confirmed that the point mutation allele is expressed at a level comparable towild-type. [MGI Ref ID J:95316]

Genotyping

Genotyping Information

Genotyping Protocols

Trp53tm4Tyj, tm2.1Tyj, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Olive KP; Tuveson DA; Ruhe ZC; Yin B; Willis NA; Bronson RT; Crowley D; Jacks T. 2004. Mutant p53 gain of function in two mouse models of Li-Fraumeni syndrome. Cell 119(6):847-60. [PubMed: 15607980]  [MGI Ref ID J:95316]

Additional References

Trp53tm2.1Tyj related

Dai C; Whitesell L; Rogers AB; Lindquist S. 2007. Heat shock factor 1 is a powerful multifaceted modifier of carcinogenesis. Cell 130(6):1005-18. [PubMed: 17889646]  [MGI Ref ID J:129386]

Doyle B; Morton JP; Delaney DW; Ridgway RA; Wilkins JA; Sansom OJ. 2010. p53 mutation and loss have different effects on tumourigenesis in a novel mouse model of pleomorphic rhabdomyosarcoma. J Pathol 222(2):129-37. [PubMed: 20662002]  [MGI Ref ID J:163599]

Kirsch DG; Dinulescu DM; Miller JB; Grimm J; Santiago PM; Young NP; Nielsen GP; Quade BJ; Chaber CJ; Schultz CP; Takeuchi O; Bronson RT; Crowley D; Korsmeyer SJ; Yoon SS; Hornicek FJ; Weissleder R; Jacks T. 2007. A spatially and temporally restricted mouse model of soft tissue sarcoma. Nat Med 13(8):992-7. [PubMed: 17676052]  [MGI Ref ID J:125101]

Marrache F; Tu SP; Bhagat G; Pendyala S; Osterreicher CH; Gordon S; Ramanathan V; Penz-Osterreicher M; Betz KS; Song Z; Wang TC. 2008. Overexpression of interleukin-1beta in the murine pancreas results in chronic pancreatitis. Gastroenterology 135(4):1277-87. [PubMed: 18789941]  [MGI Ref ID J:142524]

Morton JP; Timpson P; Karim SA; Ridgway RA; Athineos D; Doyle B; Jamieson NB; Oien KA; Lowy AM; Brunton VG; Frame MC; Evans TR; Sansom OJ. 2010. Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer. Proc Natl Acad Sci U S A 107(1):246-51. [PubMed: 20018721]  [MGI Ref ID J:156461]

Su X; Chakravarti D; Flores ER. 2013. p63 steps into the limelight: crucial roles in the suppression of tumorigenesis and metastasis. Nat Rev Cancer 13(2):136-43. [PubMed: 23344544]  [MGI Ref ID J:193489]

Timpson P; McGhee EJ; Morton JP; von Kriegsheim A; Schwarz JP; Karim SA; Doyle B; Quinn JA; Carragher NO; Edward M; Olson MF; Frame MC; Brunton VG; Sansom OJ; Anderson KI. 2011. Spatial regulation of RhoA activity during pancreatic cancer cell invasion driven by mutant p53. Cancer Res 71(3):747-57. [PubMed: 21266354]  [MGI Ref ID J:169401]

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 maintained as a live colony, heterozygotes are typically bred. Homozygotes do not breed well.

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* $2450.00
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 11 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* $3185.00
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 11 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.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.


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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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