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. Species laboratory mouse   Donating Investigator Tyler Jacks,   Massachusetts Institute of Technology

Description
Mice carrying this Trp53 (p53) R172H point mutation mimic human Li-Fraumeni Syndrome, both genotypically and phenotypically. Heterozygotes 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 a broad spectrum of tumors, particularly T-cell lymphomas, hemangiosarcomas, soft-tissue sarcomas, osteosarcomas, primitive tumors (particularly male teratocarcinomas), and a variety of epithelial carcinomas. Mutant protein is expressed at high levels in mouse embryonic fibroblasts, as determined by Western blotting.

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. Resultant mice were crossed with a protamine promoter-driven Cre strain on an undetermined background to remove the stop cassette. The strain was backcrossed to C57BL/6 approximately 5 times by the donating laboratory.

Related Strains

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
008182	B6.129S4-Trp53tm3.1Tyj/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)

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.

Trp53^tm2.1Tyj/Trp53⁺

        involves: 129S4/SvJae

• life span-post-weaning/aging
• premature death (MGI Ref ID J:95316)
  • mean life span is 15.2 months
• tumorigenesis
• increased metastatic potential (MGI Ref ID J:95316)
  • tumors metastisize more frequently than those in Trp53^tm1Tyj or Trp53^tm3.1Tyj heterozygotes
• cellular phenotype
• decreased cellular sensitivity to gamma-irradiation (MGI Ref ID J:95316)
  • resistance to gamma-irradiation induced apoptosis is increased compared to Trp53^tm1Tyj heterozygotes
• increased cell proliferation (MGI Ref ID J:95316)
  • a larger fraction of MEFs are in S phase compared to Trp53^tm1Tyj hterozygotes; however DNA damage-induced G1 arrest is intact
• skeleton phenotype
• osteopetrosis (MGI Ref ID J:95316)
  • diffuse osteopetrosis is frequently observed with osteosarcomas

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
      Other Tissues/Organs: multiple
      Skin Cancers
Oncogenes

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		Trp53tm2.1Tyj
Allele Name		targeted mutation 2.1, Tyler Jacks
Allele Type		Targeted (knock-in)
Common Name(s)		TrpR172H; p53 R172H; p53R172H;
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 Trp53tm2Tyj via cre-mediated recombination, leaving an R172H missense mutation in exon 5. Quantitative real-time PCR confirmed that the point mutation allele is expressed at a level comparable towild-type. [MGI Ref ID J:95316]

Genotyping

Genotyping Information

Genotyping Protocols

Trp53^{tm4Tyj, tm2.1Tyj}, Standard PCR

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

Trp53^tm2.1Tyj related

Dai C; Whitesell L; Rogers AB; Lindquist S. 2007. Heat shock factor 1 is a powerful multifaceted modifier of carcinogenesis. Cell 130(6):1005-18. [PubMed: 17889646]  [MGI Ref ID J:129386]

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]

Marrache F; Tu SP; Bhagat G; Pendyala S; Osterreicher CH; Gordon S; Ramanathan V; Penz-Osterreicher M; Betz KS; Song Z; Wang TC. 2008. Overexpression of interleukin-1beta in the murine pancreas results in chronic pancreatitis. Gastroenterology 135(4):1277-87. [PubMed: 18789941]  [MGI Ref ID J:142524]

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 & Husbandry	When maintained as a live colony, heterozygotes are typically bred. Homozygotes do not breed well.

Purchasing information

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

Pricing

Supply Details

Standard Supply

Cryopreserved. 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.

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Ordering and Purchasing Information

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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

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

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