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Strain Name:

B6.129S2-Trp53tm1Tyj/J

Stock Number:

002101

Availability:

Level 4

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Genes & Alleles   Trp53;   Trp53tm1Tyj;

Product Information

Strain Details

Type JAX® GEMM® Strain - Congenic
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Mutant Strain
Type JAX® GEMM® Strain - Targeted Mutation
Mating SystemHeterozygote x Heterozygote         (Female x Male)
Specieslaboratory mouse
Background Strain C57BL/6J
Donor Strain 129S2 via D3 ES cell line
Donating Investigator IMR Colony,   The Jackson Laboratory
GenerationN11F13 (20-DEC-06)

Appearance
black
Related Genotype: a/a

Strain Description
Mice homozygous for the Trp53tm1Tyj mutation show no visible phenotype but most develop tumors (principally lymphomas and osteosarcoma) at 3-6 months of age. Heterozygous mice develop tumors at about 10 months of age. These mice model some of the features of human Li-Fraumeni syndrome, a form of familial breast cancer with mutations in TRP53. Homozygous mice may produce a litter before succumbing to tumors.

Strain Development
The Trp53tm1Tyj mutant strain was developed in the laboratory of Dr. Tyler Jacks at the Center for Cancer Research at the Massachusetts Institute of Technology. The 129-derived D3 ES cell line was used. The C57BL/6J strain was produced by backcrossing the Trp53tm1Tyj mutation 10 times to C57BL/6J inbred mice.

Related Disease (OMIM) Terms

Li-Fraumeni Syndrome 1; LFS1
Mammalian Phenotype Terms assigned by genotype

Trp53tm1Tyj/Trp53+

        involves: C57BL/6
  • life span-post-weaning/aging
  • premature death (MGI Ref ID J:95318)
    • heterozygous mutants die between 150 to 750 days after birth
  • tumorigenesis
  • carcinoma (MGI Ref ID J:95318)
    • 12% of heterozygous mutants developed carcinomas, which are rare in homozygotes
  • lymphoma (MGI Ref ID J:95318)
    • 32% of heterozygous mutants developed lymphomas
  • sarcoma (MGI Ref ID J:95318)
    • 56% of heterozygous mutants developed sarcomas

Trp53tm1Tyj/Trp53tm1Tyj

        involves: C57BL/6
  • life span-post-weaning/aging
  • premature death (MGI Ref ID J:95318)
    • homozygous mutants die between ~50 to 250 days after birth
  • tumorigenesis
  • lymphoma (MGI Ref ID J:95318)
    • 56% of homozygous nulls developed lymphomas
  • sarcoma (MGI Ref ID J:95318)
    • 40% of homozygous nulls developed sarcomas
  • cellular phenotype
  • decreased cellular sensitivity to gamma-irradiation (MGI Ref ID J:95318)
    • irradiated E13.5 heterozygous embryos showed no evidence of apoptosis in the hypothalamus compared to wildtype and heterozygotes that showed a high number of apoptotic cells
  • increased cell proliferation (MGI Ref ID J:95318)
    • MEFs initially did not show any significant differences in growth rate but by day 4, grew more rapidly than wildtype or heterozygous MEFs

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

Trp53tm1Tyj/Trp53+

        involves: 129S2/SvPas * C57BL/6
  • tumorigenesis
  • increased tumor incidence (MGI Ref ID J:17728)
    • age of onset 9 months

Trp53tm1Tyj/Trp53+

        involves: 129/Sv * C57BL/6
  • life span-post-weaning/aging
  • premature death (MGI Ref ID J:135509)
    • less than 5% of mice live past two years due to cancerous tumors
  • tumorigenesis
  • increased tumor incidence (MGI Ref ID J:72391)
    • over 95% of mice have tumors by 2 years of age
    • adenoma (MGI Ref ID J:72391)
    • carcinoma (MGI Ref ID J:72391)
    • leukemia (MGI Ref ID J:135509)
      • is observed in 2.6% of mice by 24 months of age
    • lymphoma (MGI Ref ID J:72391)
      • is observed in 18.4% of mice by 24 months of age
    • sarcoma (MGI Ref ID J:72391)

Trp53tm1Tyj/Trp53+

        involves: 129S2/SvPas
  • life span-post-weaning/aging
  • premature death (MGI Ref ID J:95316)
    • mean life span is 15.4 months
  • tumorigenesis
  • increased tumor incidence (MGI Ref ID J:95316)
    • 19% have multiple tumors compared to 44% of Trp53tm3.1Tyj heterozygotes
    • carcinoma (MGI Ref ID J:95316)
      • 4 of 37 develop low grade carcinomas including 1 with a well differentiated lung carcinoma
  • cellular phenotype
  • increased cell proliferation (MGI Ref ID J:95316)
    • a larger fraction of MEFs are in S phase compared to wild type mice

Trp53tm1Tyj/Trp53tm1Tyj

        involves: 129S2/SvPas * C57BL/6
  • tumorigenesis
  • increased tumor incidence (MGI Ref ID J:17728)
    • most mice dead by 6 months
    • predominantly lymphomas with sarcomas and teratomas

Trp53tm1Tyj/Trp53tm1Tyj

        involves: 129/Sv * C57BL/6
  • life span-post-weaning/aging
  • premature death (MGI Ref ID J:72391)
    • average life span 160 days
    • 90% had succumbed to tumors and died by 7 months of age
  • tumorigenesis
  • increased tumor incidence (MGI Ref ID J:72391)
    • adenoma (MGI Ref ID J:72391)
    • carcinoma (MGI Ref ID J:72391)
    • lymphoma (MGI Ref ID J:72391)
      • thymic lymphoma (MGI Ref ID J:87501)
        • 75% of observed tumors were thymic lymphomas
    • sarcoma (MGI Ref ID J:72391)
  • cellular phenotype
  • abnormal apoptosis (MGI Ref ID J:87501)
  • chromosome breakage (MGI Ref ID J:87501)
    • aneuploidy

Trp53tm1Tyj/Trp53tm1Tyj

        involves: 129S2/SvPas
  • lethality-prenatal/perinatal
  • prenatal lethality (MGI Ref ID J:95316)
    • a slight decrease is seen in the number of females born
  • life span-post-weaning/aging
  • premature death (MGI Ref ID J:95316)
    • mean life span is 4.4 months
    • majority of mice (82%) die before 9 months of age, or are euthanized due to occurrence of obvious tumor mass
  • nervous system phenotype
  • abnormal neurogenesis (MGI Ref ID J:102702)
    • GNPs from mutants show ~50% levels of proliferation compared to Cdkn2c, Trp53-double null cells after 3 days in culture and levels of cells incorporating BrdU are still less in single mutants in tests where cells are stimulated with Shh after culture
  • tumorigenesis
  • increased tumor incidence (MGI Ref ID J:95316)
    • 32% have multiple tumors
    • T cell derived lymphoma (MGI Ref ID J:95316)
      • 66% of homozygotes display hematological malignancies, primarily T cell lymphomas
    • hemangiosarcoma (MGI Ref ID J:95316)
      • the incidence of hemangiosarcomas is 32% compared to 62% in Trp53tm1Tyj/Trp53tm2.1Tyj mice
    • medulloblastoma (MGI Ref ID J:102702)
      • 13/19 (68%) of animals receiving 4 Gy radiation at P5 or 6 develop cerebellar tumors
  • cellular phenotype
  • abnormal cell cycle checkpoint function (MGI Ref ID J:77907)
    • gamma-irradiation fails to produce an increase in the relative number of cells in G1 compared to S phase
  • decreased cellular sensitivity to ultraviolet irradiation (MGI Ref ID J:77907)
    • reduced sensitivity to UV-induced cell death in MEFs compared to wild type cells
  • increased cell proliferation (MGI Ref ID J:77907)
    • in MEFs
  • polyploidy (MGI Ref ID J:109354)
    • after irradiation with UVC light, MEFs from null mice show higher levels of polyploidy than Trp53tm2Xu homozygotes
  • hematopoietic system phenotype
  • decreased T cell apoptosis (MGI Ref ID J:109354)
    • thymocytes are essentially resistant to Trp53-mediated apoptosis
  • immune system phenotype
  • decreased T cell apoptosis (MGI Ref ID J:109354)
    • thymocytes are essentially resistant to Trp53-mediated apoptosis

Trp53tm1Tyj/Trp53tm1Tyj

        involves: 129S2/SvPas * BALB/c
  • cellular phenotype
  • increased cellular sensitivity to ionizing radiation (MGI Ref ID J:116176)
    • at P10, pattern and extent of oocyte loss in ovaries of mutants after exposure to 0.45 Gy radiation on P5 is similar to wild type and much more sever than Trp63tm2Fmc mutants

Trp53tm1Tyj/Trp53tm1Tyj

        129S6.129-Trp53tm1Tyj Rb1tm1.1Jyjw
  • life span-post-weaning/aging
  • premature death (MGI Ref ID J:102483)
    • mice become moribund from lymphoma involving various tissues within >30 weeks; mice with aggressive lymphoma have a mean survival time of 18 weeks
  • tumorigenesis
  • lymphoma (MGI Ref ID J:102483)
    • mice develop lymphomas
  • teratoma (MGI Ref ID J:102483)
    • median survival time of mice with teratomas is 7 weeks
    • no mice living beyond median survival age show extratesticular teratomas
    • testicular teratoma (MGI Ref ID J:102483)
  • digestive/alimentary phenotype
  • *normal* digestive/alimentary phenotype (MGI Ref ID J:102483)
    • after 7 days of dextran sodium sulfate treatment, mice develop large ulcers in the colon
  • growth/size phenotype
  • weight loss (MGI Ref ID J:102483)
    • with DSS treatment, double mutants have an average weight of 14% of body weight

Gene & Allele Details

Allele Symbol Trp53tm1Tyj
Allele Name targeted mutation 1, Tyler Jacks
Common Name(s) Trp53-; p53-; p53delta; p53null;
Mutation Made By Tyler Jacks,   Massachusetts Institute of Technology
Strain of Origin129S2/SvPas
ES Cell Line NameD3
ES Cell Line Strain129S2/SvPas
Gene Symbol and Name Trp53, transformation related protein 53
Chromosome 11
Gene Common Name(s) FLJ92943; LFS1; MGC112612; Tp53; p53;
General Note This mutant allele was produced by a targeted neo insertion into the Trp53 locus. Homozygotes show no visible phenotype but develop tumors at 3-6 months of age. Heterozygotes develop tumors at 10 months of age. These mice model some of the features of human Li-Fraumeni syndrome (OMIM 151623), a form of familial breast cancer with mutations in TRP53 (J:16022)(J:16023) A specific human mutation found in hepatocellular carcinomas caused by hepatitis B infection or by aflatoxin exposure has been created in amouse model, resulting in a similar gene product (J:27363).
Molecular Note A neomycin cassette replaced 40% of the coding sequences beginning with exon 2 (upstream of the translation start site) and extending into exon 6. [MGI Ref ID J:17728]

Control Information

  Allele   Control
 Trp53tm1Tyj  000664 C57BL/6J
 
  Considerations for Choosing Controls

Genotyping Protocols

Trp53tm1Tyj

Colony Maintenance

Diet Information LabDiet® 5K52/5K67

Related Strains

Strains carrying   Trp53tm1Tyj allele
002080   129-Trp53tm1Tyj/J
002103   B6;129S2-Trp53tm1Tyj/J
002526   C.129S2(B6)-Trp53tm1Tyj/J
002547   C3Ou.129S2(B6)-Trp53tm1Tyj/J
002899   FVB.129S2(B6)-Trp53tm1Tyj/J
View Strains carrying   Trp53tm1Tyj     (5 strains)

View Strains carrying other alleles of Trp53     (7 strains)

Additional Web Information

Congenic Nomenclature
Genetic Quality Control Annual Report
JAX® NOTES, Spring 2003; 489. Medulloblastoma Mouse Models.

Animal Health Reports

Room Number           AX1

Research Applications

This mouse can be used to support research in many areas including:

Trp53tm1Tyj related

Apoptosis Research
Endogenous Regulators

Cancer Research
Increased Tumor Incidence (Lymphomas)
Increased Tumor Incidence (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)
Toxicology Research (drug/compound testing)

References

Selected Reference(s)

Jacks T; Remington L; Williams BO; Schmitt EM; Halachmi S; Bronson RT; Weinberg RA. 1994. Tumor spectrum analysis in p53-mutant mice. Curr Biol 4(1):1-7. [PubMed: 7922305]  [MGI Ref ID J:17728]

Additional References

Price and Supply Information

Strain Name: B6.129S2-Trp53tm1Tyj/J
Stock Number: 002101

Price Details

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Supply Details

Standard SupplyLevel 4. Up to 10 mice. Larger quantities or custom orders arranged upon request. Expected delivery up to one to three months.
Supply Notes Shipped at a specific age in weeks. Mice at a precise age in days, littermates and retired breeders are also available.
Strains that must be genotyped are not available until five to seven weeks of age.
This strain is included in the Induced Mutant Resource Colony collection.
Genomic DNA is available for this strain from the Mouse DNA Resource.
LicensingSee General Terms and Conditions below for Licensing and Use Restrictions  
Control InformationView Control Information in Strain Details.

General Terms and Conditions

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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.

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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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