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Strain Name:

B6.129S6-Trp53tm2Xu/J

Stock Number:

007218

Availability:

Under Development for Distribution Colony

To register your interest in this strain go to the Strain Interest Form.
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General Terms and Conditions
Additional Licensing and Use Restrictions

Former Name      B6.129S-Trp53tm2Xu/J    (Changed: 15-JUL-08 )
Genes & Alleles   Trp53;   Trp53tm2Xu;

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 System+/+ sibling x Heterozygote         (Female x Male)
Specieslaboratory mouse
Donating Investigator IMR Colony,   The Jackson Laboratory
Generation?+N5 (28-JUL-08)

Strain Description
Mice homozygous for this targeted mutation are viable and fertile. They carry two phosphorylation site disruptions: Ser18 to Ala (S18A), and Ser23 to Ala (S23A). Trp53-dependent apoptosis is essentially abolished in thymocytes. These mice develop spontaneous tumors at approximately 1.5 years of age and also develop a range of malignancies that are distinct from those found in animals carrying either a single S23A mutation or a complete knockout of the gene. This mutant mouse strain may be useful in studies of phosphorylation events, cancer development and apoptosis.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Strain Development
A targeting vector containing Ser18 to Ala, and Ser23 to Ala mutations, in addition to a "floxed" PGK-Neo resistance cassette in exon 4, was injected into 129S6/SvEvTac-derived TC-1 embryonic stem (ES) cells. F1 mutant heterozygous mice were bred to CMV-Cre transgenic mice to excise the "floxed" PGK-Neo cassette. Homozyotes were created by intercrossing heterozygous mice prior to arrival at The Jackson Laboratory (as Stock No. 006980). Upon arrival, some mice were backcrossed to C57BL/6J for at least 5 generations to generate this congenic strain (Stock No. 007218).

Mammalian Phenotype Terms assigned by genotype

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

Trp53tm2Xu/Trp53tm2Xu

        involves: 129S6/SvEvTac
  • tumorigenesis
  • altered tumor susceptibility/resistance (MGI Ref ID J:109354)
    • mice are cancer prone but develop tumors in a wide spectrum of tissues, with a delayed onset compared with Trp53-null mice which develop thymic lymphomas primarily within 6 months of age
    • abnormal tumor incidence (MGI Ref ID J:109354)
      • mice develop leukemias, fibrosarcomas, granuloma and adenomas; these are rarely seen in Trp53tm1Tj homozygous mice
  • hematopoietic system phenotype
  • decreased T cell apoptosis (MGI Ref ID J:109354)
    • thymocytes are essentially resistant to Trp53-mediated apoptosis
  • decreased T cell proliferation (MGI Ref ID J:109354)
    • proliferation of thymocytes after stimulation with PMA or Ionomycin is slower than Trp53tm1Tyj cells at the later time point, but similar to wild type at the earlier time point
  • immune system phenotype
  • decreased T cell apoptosis (MGI Ref ID J:109354)
    • thymocytes are essentially resistant to Trp53-mediated apoptosis
  • decreased T cell proliferation (MGI Ref ID J:109354)
    • proliferation of thymocytes after stimulation with PMA or Ionomycin is slower than Trp53tm1Tyj cells at the later time point, but similar to wild type at the earlier time point

Gene & Allele Details

Allele Symbol Trp53tm2Xu
Allele Name targeted mutation 2, Yang Xu
Common Name(s) p53S18/23A;
Mutation Made By Yang Xu,   University of California, San Diego
Strain of Origin129S6/SvEvTac
ES Cell Line NameTC-1
ES Cell Line Strain129S6/SvEvTac
Gene Symbol and Name Trp53, transformation related protein 53
Chromosome 11
Gene Common Name(s) FLJ92943; LFS1; MGC112612; Tp53; p53;
Molecular Note Site directed mutagenesis within exon 2 generated missense mutations at codons 18 and 23, resulting in the substitutions of both serines with alanines. A single loxP site remained in intron 4 after a floxed PGK-neo cassette was excised via cre-mediated recombination. Sequencing verified that only the S18/23A mutations were present in mutant mice. [MGI Ref ID J:109354]

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Genotyping Protocols

Trp53tm2Xu

Colony Maintenance

Breeding & HusbandryMutant mice were bred to C57BL/6J mice to generate this congenic strain. When maintaining the live congenic colony, heterozygous mice are bred to wildtype siblings or to C57BL/6J inbred mice. Homozygous mice may also be bred.
Diet Information LabDiet® 5K52/5K67

Related Strains

Strains carrying   Trp53tm2Xu allele
006980   B6;129-Trp53tm2Xu/J
View Strains carrying   Trp53tm2Xu     (1 strain)

View Strains carrying other alleles of Trp53     (11 strains)

Additional Web Information

Congenic Nomenclature

Research Applications

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

Apoptosis Research
Endogenous Regulators

Cancer Research
Increased Tumor Incidence (Adenomas)
Increased Tumor Incidence (Gonadal Tumors: ovarian)
Increased Tumor Incidence (Leukemia)
Increased Tumor Incidence (Lymphomas)
Increased Tumor Incidence (Other Tissues/Organs)
Tumor Suppressor Genes

Immunology and Inflammation Research
Intracellular Signaling Molecules

Trp53 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)

Chao C; Herr D; Chun J; Xu Y. 2006. Ser18 and 23 phosphorylation is required for p53-dependent apoptosis and tumor suppression. EMBO J 25(11):2615-22. [PubMed: 16757976]  [MGI Ref ID J:109354]

Price and Supply Information

Strain Name: B6.129S6-Trp53tm2Xu/J
Stock Number: 007218
 

This strain is currently Under Development for Distribution Colony.
To register your interest in this strain go to the Strain Interest Form.

Estimated Available for Sale Date: 15-SEP-08

Please note: Estimated available for sale dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for sale depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain/interest registered.

View All Strains Under Development

Supply Details

Standard SupplyUnder Development for Distribution Colony
Supply Notes Usually shipped between four and eight weeks of age.
This strain is included in the Induced Mutant Resource Colony collection.
LicensingSee General Terms and Conditions below for Licensing and Use Restrictions  
Control InformationView Control Information in Strain Details.

General Terms and Conditions

View JAX® Mice & Services Conditions of Use.

Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.
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.

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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