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 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 (p53R172H; structural mutant homologous to human p53 codon 175). 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 R172H missense mutation into exon 5. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. The strain was maintained on a 129S4/SvJae background by the donating laboratory.

Related Strains

Strains carrying other alleles of Trp53

004301	129-Trp53tm1Holl/J
002080	129-Trp53tm1Tyj/J
008651	129S-Trp53tm3Tyj/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
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     (25 strains)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

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

Trp53^tm2Tyj/Trp53^tm2Tyj

        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

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Trp53tm2Tyj
Allele Name		targeted mutation 2, Tyler Jacks
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		LSL-Trp53R172H; p53 LSL-R172H; p53LSL(dot)R172H; p53LSL-R172H;
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 R172H missense mutation into exon 5. [MGI Ref ID J:95316]

Genotyping

Genotyping Information

Genotyping Protocols

Trp53^tm2Tyj, Separated 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

Trp53^tm2Tyj related

Bayne LJ; Beatty GL; Jhala N; Clark CE; Rhim AD; Stanger BZ; Vonderheide RH. 2012. Tumor-derived granulocyte-macrophage colony-stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic cancer. Cancer Cell 21(6):822-35. [PubMed: 22698406]  [MGI Ref ID J:189283]

Chugh R; Sangwan V; Patil SP; Dudeja V; Dawra RK; Banerjee S; Schumacher RJ; Blazar BR; Georg GI; Vickers SM; Saluja AK. 2012. A preclinical evaluation of minnelide as a therapeutic agent against pancreatic cancer. Sci Transl Med 4(156):156ra139. [PubMed: 23076356]  [MGI Ref ID J:189216]

Collins MA; Brisset JC; Zhang Y; Bednar F; Pierre J; Heist KA; Galban CJ; Galban S; di Magliano MP. 2012. Metastatic pancreatic cancer is dependent on oncogenic Kras in mice. PLoS One 7(12):e49707. [PubMed: 23226501]  [MGI Ref ID J:195686]

Colvin EK; Susanto JM; Kench JG; Ong VN; Mawson A; Pinese M; Chang DK; Rooman I; O'Toole SA; Segara D; Musgrove EA; Sutherland RL; Apte MV; Scarlett CJ; Biankin AV. 2011. Retinoid signaling in pancreatic cancer, injury and regeneration. PLoS One 6(12):e29075. [PubMed: 22220202]  [MGI Ref ID J:182325]

Cook N; Frese KK; Bapiro TE; Jacobetz MA; Gopinathan A; Miller JL; Rao SS; Demuth T; Howat WJ; Jodrell DI; Tuveson DA. 2012. Gamma secretase inhibition promotes hypoxic necrosis in mouse pancreatic ductal adenocarcinoma. J Exp Med 209(3):437-44. [PubMed: 22351932]  [MGI Ref ID J:182504]

Fendrich V; Schneider R; Maitra A; Jacobsen ID; Opfermann T; Bartsch DK. 2011. Detection of precursor lesions of pancreatic adenocarcinoma in PET-CT in a genetically engineered mouse model of pancreatic cancer. Neoplasia 13(2):180-6. [PubMed: 21403843]  [MGI Ref ID J:171634]

Frese KK; Neesse A; Cook N; Bapiro TE; Lolkema MP; Jodrell DI; Tuveson DA. 2012. nab-Paclitaxel potentiates gemcitabine activity by reducing cytidine deaminase levels in a mouse model of pancreatic cancer. Cancer Discov 2(3):260-9. [PubMed: 22585996]  [MGI Ref ID J:193075]

Gruner BM; Hahne H; Mazur PK; Trajkovic-Arsic M; Maier S; Esposito I; Kalideris E; Michalski CW; Kleeff J; Rauser S; Schmid RM; Kuster B; Walch A; Siveke JT. 2012. MALDI imaging mass spectrometry for in situ proteomic analysis of preneoplastic lesions in pancreatic cancer. PLoS One 7(6):e39424. [PubMed: 22761793]  [MGI Ref ID J:187923]

Hingorani SR; Wang L; Multani AS; Combs C; Deramaudt TB; Hruban RH; Rustgi AK; Chang S; Tuveson DA. 2005. Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell 7(5):469-83. [PubMed: 15894267]  [MGI Ref ID J:98936]

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]

Kasinski AL; Slack FJ. 2012. miRNA-34 prevents cancer initiation and progression in a therapeutically resistant K-ras and p53-induced mouse model of lung adenocarcinoma. Cancer Res 72(21):5576-87. [PubMed: 22964582]  [MGI Ref ID J:191425]

Koso H; Takeda H; Yew CC; Ward JM; Nariai N; Ueno K; Nagasaki M; Watanabe S; Rust AG; Adams DJ; Copeland NG; Jenkins NA. 2012. Transposon mutagenesis identifies genes that transform neural stem cells into glioma-initiating cells. Proc Natl Acad Sci U S A 109(44):E2998-3007. [PubMed: 23045694]  [MGI Ref ID J:190371]

Lampson BL; Kendall SD; Ancrile BB; Morrison MM; Shealy MJ; Barrientos KS; Crowe MS; Kashatus DF; White RR; Gurley SB; Cardona DM; Counter CM. 2012. Targeting eNOS in pancreatic cancer. Cancer Res 72(17):4472-82. [PubMed: 22738914]  [MGI Ref ID J:191028]

Lehtonen S; Tienari J; Londesborough A; Pirvola U; Ora A; Reima I; Lehtonen E. 2008. CD2-associated protein is widely expressed and differentially regulated during embryonic development. Differentiation 76(5):506-17. [PubMed: 18177421]  [MGI Ref ID J:135527]

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]

Olive KP; Jacobetz MA; Davidson CJ; Gopinathan A; McIntyre D; Honess D; Madhu B; Goldgraben MA; Caldwell ME; Allard D; Frese KK; Denicola G; Feig C; Combs C; Winter SP; Ireland-Zecchini H; Reichelt S; Howat WJ; Chang A; Dhara M; Wang L; Ruckert F; Grutzmann R; Pilarsky C; Izeradjene K; Hingorani SR; Huang P; Davies SE; Plunkett W; Egorin M; Hruban RH; Whitebread N; McGovern K; Adams J; Iacobuzio-Donahue C; Griffiths J; Tuveson DA. 2009. Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science 324(5933):1457-61. [PubMed: 19460966]  [MGI Ref ID J:149213]

Olson P; Chu GC; Perry SR; Nolan-Stevaux O; Hanahan D. 2011. Imaging guided trials of the angiogenesis inhibitor sunitinib in mouse models predict efficacy in pancreatic neuroendocrine but not ductal carcinoma. Proc Natl Acad Sci U S A 108(49):E1275-84. [PubMed: 22084065]  [MGI Ref ID J:180399]

Provenzano PP; Cuevas C; Chang AE; Goel VK; Von Hoff DD; Hingorani SR. 2012. Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma. Cancer Cell 21(3):418-29. [PubMed: 22439937]  [MGI Ref ID J:189345]

Reichert M; Takano S; von Burstin J; Kim SB; Lee JS; Ihida-Stansbury K; Hahn C; Heeg S; Schneider G; Rhim AD; Stanger BZ; Rustgi AK. 2013. The Prrx1 homeodomain transcription factor plays a central role in pancreatic regeneration and carcinogenesis. Genes Dev 27(3):288-300. [PubMed: 23355395]  [MGI Ref ID J:193476]

Seidler B; Schmidt A; Mayr U; Nakhai H; Schmid RM; Schneider G; Saur D. 2008. A Cre-loxP-based mouse model for conditional somatic gene expression and knockdown in vivo by using avian retroviral vectors. Proc Natl Acad Sci U S A 105(29):10137-42. [PubMed: 18621715]  [MGI Ref ID J:140423]

Szabova L; Yin C; Bupp S; Guerin TM; Schlomer JJ; Householder DB; Baran ML; Yi M; Song Y; Sun W; McDunn JE; Martin PL; Van Dyke T; Difilippantonio S. 2012. Perturbation of Rb, p53, and Brca1 or Brca2 cooperate in inducing metastatic serous epithelial ovarian cancer. Cancer Res 72(16):4141-53. [PubMed: 22617326]  [MGI Ref ID J:189304]

Tuveson DA; Hingorani SR. 2005. Ductal pancreatic cancer in humans and mice. Cold Spring Harb Symp Quant Biol 70:65-72. [PubMed: 16869739]  [MGI Ref ID J:116752]

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]

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]

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 & Husbandry	When maintained as a live colony, heterozygotes may be bred. Homozygous mice develop tumors.

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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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