Strain Name:

B6.129S4-Trp53tm3.1Tyj/J

Stock Number:

008182

Availability:

Cryopreserved - Ready for recovery

Use Restrictions Apply, see Terms of Use
These targeted mutant mice carry a R270H missense mutation in exon 8 of the Trp53, transformation related protein 53 gene. Heterozygous mice 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 an array of tumor types including a variety of hematological tumors (particularly T-cell lymphomas), hemangiosarcomas, soft-tissue sarcomas, ostersarcomas, primitive tumors (particularly male teratocarcinomas), and a variety of epithelial carcinomas. Homozygotes have a mean survival time of 4.5 months. This strain may be useful in studies of cancer and Li-Fraumeni Syndrome.

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 Investigator Tyler Jacks,   Massachusetts Institute of Technology

Description
These targeted mutant mice carry a R270H missense mutation in exon 8 of the gene. Heterozygous mice 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 an array of tumor types including a variety of hematological tumors (particularly T-cell lymphomas), hemangiosarcomas, soft-tissue sarcomas, ostersarcomas, primitive tumors (particularly male teratocarcinomas), and a variety of epithelial carcinomas. Homozygotes have a mean survival time of 4.5 months. Mutant protein is expressed in all of the places that wildtype protein is expressed in normal tissues. Irradiation or DNA damage leads to substantially increased protein levels. Expression is also upregulated in some tumor types. This strain may be useful in studies of cancer and Li-Fraumeni Syndrome.

Related Strains

View Strains carrying other alleles of Trp53     (21 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms
Li-Fraumeni Syndrome 1; LFS1 - Models with phenotypic similarity to human disease where etiologies involve orthologs.1
1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
View Mammalian Phenotype Terms

Mammalian Phenotype Terms
      assigned by genotype

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

Trp53tm3.1Tyj/Trp53+

        involves: 129S4/SvJae
  • life span-post-weaning/aging
  • premature death (MGI Ref ID J:95316)
    • mean life span is 15.8 months
  • tumorigenesis
  • increased metastatic potential (MGI Ref ID J:95316)
    • compared to Trp53tm1Tyj
  • increased tumor incidence (MGI Ref ID J:95316)
    • the incidence of carcinomas is increased compared to Trp53tm1Tyj heterozygotes
    • 5 of 36 develop squamous cell carcinomas and a single case each of transitional cell renal carcinoma and intestinal carcinoma are seen
    • B cell derived lymphoma (MGI Ref ID J:95316)
      • 5 of 36 develop B cell lymphomas generally arising in the spleen or mesenteric lymph nodes
    • carcinoma (MGI Ref ID J:95316)
      • the incidence of carcinomas is increased compared to Trp53tm1Tyj heterozygotes
      • a single case each of transitional cell renal carcinoma and intestinal carcinoma are seen
      • hepatocellular carcinoma (MGI Ref ID J:95316)
        • 2 of 36 develop hepatocellular carcinomas
      • lung adenocarcinoma (MGI Ref ID J:95316)
        • 7 of 36 develop lung adenocarcinomas, several with malignant features commonly seen in human lung adenocarcinomaincluding nuclear atypia (5 of 7), desmoplasia (4 of 7), and metaplasias (2 of 7)
      • squamous cell carcinoma (MGI Ref ID J:95316)
        • 5 of 36 develop squamous cell carcinomas
  • cellular phenotype
  • decreased cellular sensitivity to gamma-irradiation (MGI Ref ID J:95316)
    • resistance to gamma-irradiation induced apoptosis is increased compared to Trp53tm1Tyj hterozygotes
  • increased cell proliferation (MGI Ref ID J:95316)
    • a larger fraction of MEFs are in S phase compared to Trp53tm1Tyj hterozygotes; however DNA damage-induced G1 arrest is intact

Trp53tm3.1Tyj/Trp53+

        involves: 129S4/SvJae * SKH1
  • tumorigenesis
  • mammary adenocarcinoma (MGI Ref ID J:121734)
    • in 2 mice
  • skin tumor (MGI Ref ID J:121734)
    • whether spontaneous or induced, mice develop epithelial, proliferative lesions forming a continuum from nonneoplastic squamous keratosis and acanthosis to squamous cell papillomas, actinic keratosis and keratoacanthoma with increasing degrees of atypia and dysplasia, carcinoma in situ, up to invasive squamous cell carcinoma
  • skin/coat/nails phenotype
  • skin tumor (MGI Ref ID J:121734)
    • whether spontaneous or induced, mice develop epithelial, proliferative lesions forming a continuum from nonneoplastic squamous keratosis and acanthosis to squamous cell papillomas, actinic keratosis and keratoacanthoma with increasing degrees of atypia and dysplasia, carcinoma in situ, up to invasive squamous cell carcinoma
View Research Applications

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

Cancer Research
Increased Tumor Incidence
      Lymphomas: B cell lymphomas

Trp53 related

Apoptosis Research
Endogenous Regulators

Cancer Research
Increased Tumor Incidence
      Lymphomas
      Other Tissues/Organs: osteosarcoma
Toxicology
Tumor Suppressor Genes

Immunology and Inflammation Research
Intracellular Signaling Molecules

Mouse/Human Gene Homologs
Li-Fraumeni syndrome

Research Tools
Toxicology Research
      B and T cell deficiency, xenograft transplant host
      drug/compound testing

Genes & Alleles

Gene & Allele Information

 
Allele Symbol Trp53tm3.1Tyj
Allele Name targeted mutation 3.1, Tyler Jacks
Allele Type Targeted (knock-in)
Common Name(s) Trp53R270H; p53 R270H; p53H; p53R270H;
Mutation Made By Tyler Jacks,   Massachusetts Institute of Technology
Strain of Origin129S4/SvJae
ES Cell Line NameJ1
ES Cell Line Strain129S4/SvJae
Gene Symbol and Name Trp53, transformation related protein 53
Chromosome 11
Gene Common Name(s) FLJ92943; LFS1; MGC112612; p53;
Molecular Note The loxP flanked stop cassette was removed from Trp53tm3Tyj via cre-mediated recombination, leaving an R270H missense mutation in exon 8. Quantitative real-time PCR confirmed that the point mutation allele was expressed at a level comparable to wild-type. [MGI Ref ID J:95316]

Genotyping

Genotyping Information

Genotyping Protocols

Trp53tm3.1Tyj, Pyrosequencing

Helpful Links

Genotyping resources and troubleshooting

References

References

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

Trp53tm3.1Tyj related

Bertout JA; Patel SA; Fryer BH; Durham AC; Covello KL; Olive KP; Goldschmidt MH; Simon MC. 2009. Heterozygosity for hypoxia inducible factor 1alpha decreases the incidence of thymic lymphomas in a p53 mutant mouse model. Cancer Res 69(7):3213-20. [PubMed: 19293180]  [MGI Ref ID J:147359]

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]

Tian H; Callahan CA; DuPree KJ; Darbonne WC; Ahn CP; Scales SJ; de Sauvage FJ. 2009. Hedgehog signaling is restricted to the stromal compartment during pancreatic carcinogenesis. Proc Natl Acad Sci U S A 106(11):4254-9. [PubMed: 19246386]  [MGI Ref ID J:146777]

Wijnhoven SW; Speksnijder EN; Liu X; Zwart E; vanOostrom CT; Beems RB; Hoogervorst EM; Schaap MM; Attardi LD; Jacks T; van Steeg H; Jonkers J; de Vries A. 2007. Dominant-negative but not gain-of-function effects of a p53.R270H mutation in mouse epithelium tissue after DNA damage. Cancer Res 67(10):4648-56. [PubMed: 17510390]  [MGI Ref ID J:121734]

Wijnhoven SW; Zwart E; Speksnijder EN; Beems RB; Olive KP; Tuveson DA; Jonkers J; Schaap MM; van den Berg J; Jacks T; van Steeg H; de Vries A. 2005. Mice expressing a mammary gland-specific R270H mutation in the p53 tumor suppressor gene mimic human breast cancer development. Cancer Res 65(18):8166-73. [PubMed: 16166291]  [MGI Ref ID J:101617]

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

Colony Maintenance

Breeding & HusbandryWhen maintained as a live colony, heterozygotes may be bred. Homozygotes can breed, but have a shortened lifespan (~4.5 months).

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Pricing for USA, Canada and Mexico shipping destinations View International pricing
Price (US dollars $)
Cryorecovery Fee $1900.00
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.

Additional Supply Details

Pricing for International shipping destinations View USA Canada and Mexico pricing
Price (US dollars $)
Cryorecovery Fee $2470.00
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.

Additional Supply Details

Supply Details

Standard SupplyCryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.
Supply Notes
  • Cryorecovery - Standard.
    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. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 13 and 16 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).

  • This strain is included in the Induced Mutant Resource Colony collection.

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.


See Terms of Use tab for General Terms and Conditions


The Jackson Laboratory's Genotype Promise

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.
Ordering and Purchasing Information

      Purchasing Information
      JAX® Mice Orders
      Surgical Services

Contact Information
Orders & Technical Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use


General Terms and Conditions


OncoMouse® requires a license from DuPont, see Licenses for Strains with OncoMouse® Technology.
P53 Mice are subject to U.S. 5,569,824 and corresponding license requirements.

Contact information

General inquiries

Contracts Administration

phone:207-288-6470
fax:207-288-6655

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED “AS IS”. JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. In purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.


(3.12)