|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 Dr. Tyler Jacks, Massachusetts Institute of Technology
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.
A targeting vector was designed to place a loxP-flanked stop cassette in intron 1 and an R270H missense mutation into exon 8. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Resultant mice were crossed with a protamine promoter-driven Cre strain to remove the stop cassette. The strain was backcrossed to a C57BL/6 background approximately ten times by the donating laboratory.
Strains carrying other alleles of Trp53
022070 129-Trp53tm1Att/J 004301 129-Trp53tm1Holl/J 002080 129-Trp53tm1Tyj/J 018431 129-Trp53tm3Att/J 021984 129-Trp53tm4Att/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 011109 B6.Cg-Trp53tm2Glo/Kvm 017767 B6;129-Trp53tm1.1Dgk/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 017530 STOCK Igs2tm2(ACTB-tdTomato,-EGFP)Luo Trp53tm1Tyj Nf1tm1Par/J 012620 STOCK Trp53tm1Brd Brca1tm1Aash Tg(LGB-cre)74Acl/J 003262 STOCK Tg(Trp53A135V)L3Ber/JView Strains carrying other alleles of Trp53 (27 strains)
View Related Disease (OMIM) TermsRelated 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).
- 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; CPP (TP53)
View Mammalian Phenotype TermsMammalian Phenotype Terms provided by MGIassigned by genotype
The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.
- premature death
- mean life span is 15.8 months (MGI Ref ID J:95316)
- increased metastatic potential
- compared to Trp53tm1Tyj (MGI Ref ID J:95316)
- increased tumor incidence (MGI Ref ID J:95316)
- increased B cell derived lymphoma incidence
- 5 of 36 develop B cell lymphomas generally arising in the spleen or mesenteric lymph nodes (MGI Ref ID J:95316)
- increased carcinoma incidence
- increased hepatocellular carcinoma incidence
- 2 of 36 develop hepatocellular carcinomas (MGI Ref ID J:95316)
- increased lung adenocarcinoma incidence
- 7 of 36 develop lung adenocarcinomas, several with malignant features commonly seen in human lung adenocarcinoma including nuclear atypia (5 of 7), desmoplasia (4 of 7), and metaplasias (2 of 7) (MGI Ref ID J:95316)
- increased squamous cell carcinoma incidence
- 5 of 36 develop squamous cell carcinomas (MGI Ref ID J:95316)
- cellular phenotype
- decreased cellular sensitivity to gamma-irradiation
- resistance to gamma-irradiation induced apoptosis is increased compared to Trp53tm1Tyj hterozygotes (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)
Trp53tm3.1Tyj/Trp53+involves: 129S4/SvJae * SKH1
- increased mammary adenocarcinoma incidence
- in 2 mice (MGI Ref ID J:121734)
- increased skin tumor incidence
- 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 (MGI Ref ID J:121734)
- integument phenotype
- increased skin tumor incidence
- 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 (MGI Ref ID J:121734)View Research ApplicationsResearch ApplicationsThis mouse can be used to support research in many areas including:
Increased Tumor Incidence
Lymphomas: B cell lymphomas
|Allele Name||targeted mutation 3.1, Tyler Jacks|
|Common Name(s)||Trp53R270H; p53 R270H; p53H; p53R270H;|
|Mutation Made By||Dr. Tyler Jacks, Massachusetts Institute of Technology|
|Strain of Origin||129S4/SvJae|
|ES Cell Line Name||J1|
|ES Cell Line Strain||129S4/SvJae|
|Promoter||Trp53, transformation related protein 53, mouse, laboratory|
|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]|
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]
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]
McFadden DG; Vernon A; Santiago PM; Martinez-McFaline R; Bhutkar A; Crowley DM; McMahon M; Sadow PM; Jacks T. 2014. p53 constrains progression to anaplastic thyroid carcinoma in a Braf-mutant mouse model of papillary thyroid cancer. Proc Natl Acad Sci U S A 111(16):E1600-9. [PubMed: 24711431] [MGI Ref ID J:208854]
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]
Rahrmann EP; Moriarity BS; Otto GM; Watson AL; Choi K; Collins MH; Wallace M; Webber BR; Forster CL; Rizzardi AE; Schmechel SC; Ratner N; Largaespada DA. 2014. Trp53 Haploinsufficiency Modifies EGFR-Driven Peripheral Nerve Sheath Tumorigenesis. Am J Pathol 184(7):2082-98. [PubMed: 24832557] [MGI Ref ID J:211653]
Rahrmann EP; Watson AL; Keng VW; Choi K; Moriarity BS; Beckmann DA; Wolf NK; Sarver A; Collins MH; Moertel CL; Wallace MR; Gel B; Serra E; Ratner N; Largaespada DA. 2013. Forward genetic screen for malignant peripheral nerve sheath tumor formation identifies new genes and pathways driving tumorigenesis. Nat Genet 45(7):756-66. [PubMed: 23685747] [MGI Ref ID J:201844]
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]
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]
Vinall RL; Chen JQ; Hubbard NE; Sulaimon SS; Shen MM; Devere White RW; Borowsky AD. 2012. Initiation of prostate cancer in mice by Tp53R270H: evidence for an alternative molecular progression. Dis Model Mech 5(6):914-20. [PubMed: 22563073] [MGI Ref ID J:191153]
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]
Wu R; Baker SJ; Hu TC; Norman KM; Fearon ER; Cho KR. 2013. Type I to type II ovarian carcinoma progression: mutant Trp53 or Pik3ca confers a more aggressive tumor phenotype in a mouse model of ovarian cancer. Am J Pathol 182(4):1391-9. [PubMed: 23499052] [MGI Ref ID J:195346]
de Vries A; Flores ER; Miranda B; Hsieh HM; van Oostrom CT; Sage J; Jacks T. 2002. Targeted point mutations of p53 lead to dominant-negative inhibition of wild-type p53 function. Proc Natl Acad Sci U S A 99(5):2948-53. [PubMed: 11867759] [MGI Ref ID J:126915]
Animal Health ReportsProduction of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.
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|
Cryopreserved Mice - Ready for Recovery
Price (US dollars $) Cryorecovery* $2140.00
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.
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|
Cryopreserved Mice - Ready for Recovery
Price (US dollars $) Cryorecovery* $2782.00
Cryorecovery - Standard.
Progeny testing is not required.
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