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| 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. | |||||||||||||||
Type Congenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory 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.
Strains carrying other alleles of Trp53
004301 129-Trp53tm1Holl/J 002080 129-Trp53tm1Tyj/J 008652 129S-Trp53tm2Tyj/J 008651 129S-Trp53tm3Tyj/J 008462 B6.129P2-Trp53tm1Brn/J 002101 B6.129S2-Trp53tm1Tyj/J 008183 B6.129S4(Cg)-Trp53tm2.1Tyj/J 007218 B6.129S6-Trp53tm2Xu/J 007962 B6.FVB-Tg(MMTV-neu/OT-I/OT-II)CBnel Tg(Trp53R172H)8512Jmr/J 008045 B6;129-Trp53tm2Holl/J 006980 B6;129-Trp53tm2Xu/J 008191 B6;129S2-Trp53tm1Tyj Nf1tm1Tyj/J 002103 B6;129S2-Trp53tm1Tyj/J 008181 B6;129S4-Trp53tm4Tyj/J 008361 B6;129S4-Trp53tm5Tyj/J 002526 C.129S2(B6)-Trp53tm1Tyj/J 002547 C3Ou.129S2(B6)-Trp53tm1Tyj/J 002899 FVB.129S2(B6)-Trp53tm1Tyj/J 002659 FVB/N-Tg(Trp53R172H)8512Jmr/J 002660 FVB/N-Tg(Trp53R172L)4491Jmr/J 003262 STOCK Tg(Trp53A135V)L3Ber/J View Strains carrying other alleles of Trp53 (21 strains)
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:
Trp53 relatedCancer Research
Increased Tumor Incidence
Lymphomas: B cell lymphomas
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
| 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 Origin | 129S4/SvJae | ||
| ES Cell Line Name | J1 | ||
| ES Cell Line Strain | 129S4/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 Protocols
Trp53tm3.1Tyj, Pyrosequencing
Helpful Links
Genotyping resources and troubleshooting
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]
Trp53tm3.1Tyj relatedBertout 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]
Colony Maintenance
Breeding & Husbandry When maintained as a live colony, heterozygotes may be bred. Homozygotes can breed, but have a shortened lifespan (~4.5 months).
| Pricing for USA, Canada and Mexico shipping destinations |
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Animals Provided
Price (US dollars $) Cryorecovery Fee $1900.00 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.
| Pricing for International shipping destinations |
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Animals Provided
Price (US dollars $) Cryorecovery Fee $2470.00 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 for further information. |
|---|---|
| Supply Notes |
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Purchasing Information
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Contact Information
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