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 Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse   Donating Investigator Tyler Jacks,   Massachusetts Institute of Technology

Description
Mice homozygous for this S23A point mutation are viable and fertile. Cells from the mice, including thymocytes and neurons in the cerebellum, exhibit defective apoptosis in response to DNA damage and exhibit partially impaired TRP53 (p53) stabilization. Mice develop increased lymphomas (especially B-cell lineage) and other tumors between one and two years of age.

Development
A targeting vector was designed to introduce a Ser23Ala point mutation to exon 2 of the gene and place a loxP-flanked puromycin resistance cassette in reverse orientation in intron 1. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Cre recombinase was introduced to targeted ES cells by transient transfection to delete the puromycin cassette. The strain has been maintained on a mixed 129S4/SvJae and C57BL/6 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
008183	B6.129S4(Cg)-Trp53tm2.1Tyj/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
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 Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Trp53^tm4Tyj/Trp53^tm4Tyj

        involves: 129S4/SvJae * C57BL/6

• life span-post-weaning/aging
• premature death (MGI Ref ID J:92917)
  • median survival time (444 days) is reduced compared to wild-type but increased compared to Trp53 null homozygotes
• tumorigenesis
• B cell derived lymphoma (MGI Ref ID J:92917)
  • a variety of B-cell derived tumors are seen in 62% of mutants including follicular, diffuse large cell, and marginal zone as well as plasmacytomas
• sarcoma (MGI Ref ID J:92917)
  • 3 mutants had sarcomas including 2 with hstiocytic sarcoma and 1 with hemangiosarcoma
  • in addition single cases of lung adenoma, lung adenocarcinoma, hepatoma, and hair matrix tumor were seen
• cellular phenotype
• decreased cellular sensitivity to gamma-irradiation (MGI Ref ID J:92917)
  • resistance to ionizing radiation-induced apoptosis of cultured thymocytes and in vivo splenic B-cells and the external granule layer of the developing cerebellum is seen

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

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		Trp53tm4Tyj
Allele Name		targeted mutation 4, Tyler Jacks
Allele Type		Targeted (knock-in)
Common Name(s)		S23A;
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		A serine to alanine mutation was created at position 23 in exon 2. Transient cre recombinase expression excised a floxed puromycin resistance cassette that was introduced with the mutation. RT-PCR of mutant MEFs confirmed correct targeting. [MGI Ref ID J:92917]

Genotyping

Genotyping Information

Genotyping Protocols

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

Helpful Links

Genotyping resources and troubleshooting

References

References

Selected Reference(s)

MacPherson D; Kim J; Kim T; Rhee BK; Van Oostrom CT; DiTullio RA; Venere M; Halazonetis TD; Bronson R; De Vries A; Fleming M; Jacks T. 2004. Defective apoptosis and B-cell lymphomas in mice with p53 point mutation at Ser 23. EMBO J 23(18):3689-99. [PubMed: 15343266]  [MGI Ref ID J:92917]

Additional References

Trp53^tm4Tyj related

El-Dahr SS; Aboudehen K; Dipp S. 2008. Bradykinin B2 receptor null mice harboring a Ser23-to-Ala substitution in the p53 gene are protected from renal dysgenesis. Am J Physiol Renal Physiol 295(5):F1404-13. [PubMed: 18753293]  [MGI Ref ID J:140998]

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 or homozygotes may be bred.

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.

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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.

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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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Terms of Use

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P53 Mice are subject to U.S. 5,569,824 and corresponding license requirements.

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