Type Coisogenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Donating Investigator Dr. Tyler Jacks, Massachusetts Institute of Technology Description
These mice carry a conditional point-mutant allele of the transformation related protein 53 gene (p53R270H; contact mutant homologous to human p53R273H). The conditional allele is functionally equivalent to a null mutation. Mice have all the phenotypic issues of p53 knockout mice and therefore have some decreased viability of homozygotes. Cre-mediated recombination leads to deletion of a transcriptional termination sequence (Lox-Stop-Lox) and expression of the oncogenic protein.Development
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. The strain was maintained on a 129S4 background by the donating laboratory.
Strains carrying other alleles of Trp53
004301 129-Trp53tm1Holl/J 002080 129-Trp53tm1Tyj/J 008652 129S-Trp53tm2Tyj/J 008462 B6.129P2-Trp53tm1Brn/J 002101 B6.129S2-Trp53tm1Tyj/J 008183 B6.129S4(Cg)-Trp53tm2.1Tyj/J 008182 B6.129S4-Trp53tm3.1Tyj/J 007218 B6.129S6-Trp53tm2Xu/J 011109 B6.Cg-Trp53tm2Glo/Kvm 018285 B6.Cg-Tyrc-2J Trp53tm1Tyj Hrhr/J 007962 B6.FVB-Tg(MMTV-neu/OT-I/OT-II)CBnel Tg(Trp53R172H)8512Jmr/J 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 Iis2tm2(ACTB-tdTomato,-EGFP)Luo Trp53tm1Tyj Nf1tm1Par/J 012620 STOCK Trp53tm1Brd Brca1tm1Aash Tg(LGB-cre)74Acl/J 003262 STOCK Tg(Trp53A135V)L3Ber/J View Strains carrying other alleles of Trp53 (26 strains)
Introduction to Cre-lox technology
View Related Disease (OMIM) Terms
Related Disease (OMIM) Terms provided by MGI
- 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)
Li-Fraumeni Syndrome 1; LFS1 (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
Trp53tm3Tyj/Trp53tm3Tyj
involves: 129S4/SvJae (conditional)
- cellular phenotype
- early cellular replicative senescence
- ovarian surface epithelium cells transfected with a cre-expressing adenovirus exhibit very limited proliferation potential and undergo senescence sooner than control cells that become immortalized (MGI Ref ID J:175978)
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:
Apoptosis Research
Endogenous Regulators
Cancer Research
Increased Tumor Incidence
Lymphomas
Other Tissues/Organs
Other Tissues/Organs: osteosarcoma
Toxicology
Tumor Suppressor Genes
Immunology, Inflammation and Autoimmunity Research
Intracellular Signaling Molecules
Research Tools
Cre-lox System
loxP-flanked Sequences
Toxicology Research
drug/compound testing
| Allele Symbol | Trp53tm3Tyj | ||
|---|---|---|---|
| Allele Name | targeted mutation 3, Tyler Jacks | ||
| Allele Type | Targeted (Floxed/Frt) | ||
| Common Name(s) | p53 LSL-R270H; p53LSL•R270H; p53LSL-R270H; | ||
| 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 | ||
| Gene Symbol and Name | Trp53, transformation related protein 53 | ||
| Chromosome | 11 | ||
| Gene Common Name(s) | BCC7; LFS1; P53; p44; | ||
| Molecular Note | A targeting construct was designed to insert a loxP flanked stop cassette into intron 1 and an R270H missense mutation into exon 8. [MGI Ref ID J:95316] | ||
Genotyping Protocols
Trp53tm3TyjLox-STOP-Lox,Separated MCA
Trp53tm3TyjPyro, Pyrosequencing
Trp53tm3TyjLox-STOP-Lox, Separated PCR
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]
Trp53tm3Tyj relatedCollisson EA; Trejo CL; Silva JM; Gu S; Korkola JE; Heiser LM; Charles RP; Rabinovich BA; Hann B; Dankort D; Spellman PT; Phillips WA; Gray JW; McMahon M. 2012. A central role for RAF-->MEK-->ERK signaling in the genesis of pancreatic ductal adenocarcinoma. Cancer Discov 2(8):685-93. [PubMed: 22628411] [MGI Ref ID J:193065]
Hwang CI; Matoso A; Corney DC; Flesken-Nikitin A; Korner S; Wang W; Boccaccio C; Thorgeirsson SS; Comoglio PM; Hermeking H; Nikitin AY. 2011. Wild-type p53 controls cell motility and invasion by dual regulation of MET expression. Proc Natl Acad Sci U S A 108(34):14240-5. [PubMed: 21831840] [MGI Ref ID J:175978]
Jackson EL; Olive KP; Tuveson DA; Bronson R; Crowley D; Brown M; Jacks T. 2005. The differential effects of mutant p53 alleles on advanced murine lung cancer. Cancer Res 65(22):10280-8. [PubMed: 16288016] [MGI Ref ID J:103407]
Keng VW; Villanueva A; Chiang DY; Dupuy AJ; Ryan BJ; Matise I; Silverstein KA; Sarver A; Starr TK; Akagi K; Tessarollo L; Collier LS; Powers S; Lowe SW; Jenkins NA; Copeland NG; Llovet JM; Largaespada DA. 2009. A conditional transposon-based insertional mutagenesis screen for genes associated with mouse hepatocellular carcinoma. Nat Biotechnol 27(3):264-74. [PubMed: 19234449] [MGI Ref ID J:147264]
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]
Shakya R; Gonda T; Quante M; Salas M; Kim S; Brooks J; Hirsch S; Davies J; Cullo A; Olive K; Wang TC; Szabolcs M; Tycko B; Ludwig T. 2013. Hypomethylating therapy in an aggressive stroma-rich model of pancreatic carcinoma. Cancer Res 73(2):885-96. [PubMed: 23204224] [MGI Ref ID J:194376]
Skoulidis F; Cassidy LD; Pisupati V; Jonasson JG; Bjarnason H; Eyfjord JE; Karreth FA; Lim M; Barber LM; Clatworthy SA; Davies SE; Olive KP; Tuveson DA; Venkitaraman AR. 2010. Germline Brca2 heterozygosity promotes Kras(G12D) -driven carcinogenesis in a murine model of familial pancreatic cancer. Cancer Cell 18(5):499-509. [PubMed: 21056012] [MGI Ref ID J:166678]
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]
Winslow MM; Dayton TL; Verhaak RG; Kim-Kiselak C; Snyder EL; Feldser DM; Hubbard DD; DuPage MJ; Whittaker CA; Hoersch S; Yoon S; Crowley D; Bronson RT; Chiang DY; Meyerson M; Jacks T. 2011. Suppression of lung adenocarcinoma progression by Nkx2-1. Nature 473(7345):101-4. [PubMed: 21471965] [MGI Ref ID J:171810]
Animal Health Reports
Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.Colony Maintenance
Breeding & Husbandry When maintained as a live colony, heterozygotes may be bred. Homozygous mice develop tumors.
| Pricing for USA, Canada and Mexico shipping destinations |
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Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2450.00 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 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 |
|
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $3185.00 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 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).
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Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.
- Use of MICE by companies or for-profit entities requires a license prior to shipping.
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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