Overview

This targeted mutation of Trp53 (transformation related protein 53) contains two phosphorylation site disruptions: Ser18 to Ala (S18A), and Ser23 to Ala (S23A). Trp53-dependent apoptosis is essentially abolished in thymocytes from mice homozygous for this allele. This mutant mouse strain may be useful in studies of phosphorylation events, cancer development and apoptosis.

Donating Investigator

IMR Colony, The Jackson Laboratory

Genetic overview

Genetic Background	Generation

Trp53^tm2Xu

Allele Type	Gene Symbol	Gene Name
Targeted	Trp53	transformation related protein 53

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Research Applications

Cancer Research
Immunology, Inflammation and Autoimmunity Research
Apoptosis Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed 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.

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 five generations to generate this congenic strain (Stock No. 007218).

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

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):2615-22PubMed: 16757976 MGI: J:109354

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Genetics

Trp53^tm2Xu

Allele Symbol: Trp53^tm2Xu

Allele Name	targeted mutation 2, Yang Xu
Allele Type	Targeted
Allele Synonym(s)	p53^S18/23A
Gene Symbol and Name	Trp53, transformation related protein 53
Gene Synonym(s)
Promoter	Trp53, transformation related protein 53, mouse, laboratory
Strain of Origin	129S6/SvEvTac
Chromosome	11
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.
Mutations Made By	Yang Xu, University of California, San Diego

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Cancer Research
- Increased Tumor Incidence
  - Other Tissues/Organs
  - Gonadal Tumors
  - Adenomas
  - Gonadal Tumors: ovarian
  - Leukemia
  - Lymphomas
- Tumor Suppressor Genes
Immunology, Inflammation and Autoimmunity Research
- Intracellular Signaling Molecules
Apoptosis Research
- Endogenous Regulators

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Trp53^tm2Xu/Trp53^tm2Xu
involves: 129S6/SvEvTac

cellular phenotype

decreased T cell apoptosis
- thymocytes are essentially resistant to Trp53-mediated apoptosis

decreased T cell proliferation
- proliferation of thymocytes after stimulation with PMA or Ionomycin is slower than Trp53^tm1Tyj cells at the later time point, but similar to wild-type at the earlier time point

hematopoietic system phenotype

decreased T cell apoptosis
- thymocytes are essentially resistant to Trp53-mediated apoptosis

decreased T cell proliferation
- proliferation of thymocytes after stimulation with PMA or Ionomycin is slower than Trp53^tm1Tyj cells at the later time point, but similar to wild-type at the earlier time point

immune system phenotype

decreased T cell apoptosis
- thymocytes are essentially resistant to Trp53-mediated apoptosis

decreased T cell proliferation
- proliferation of thymocytes after stimulation with PMA or Ionomycin is slower than Trp53^tm1Tyj cells at the later time point, but similar to wild-type at the earlier time point

neoplasm

increased tumor incidence
- mice develop leukemias, fibrosarcomas, granuloma and adenomas; these are rarely seen in Trp53^tm1Tyj homozygous mice

increased tumor latency
- 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

References

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):2615-22PubMed: 16757976 MGI: J:109354

Additional - Trp53^tm2Xu related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Trp53
- Genotyping resources and troubleshooting
Breeding Considerations

Mutant mice were bred to C57BL/6J mice to generate this congenic strain. When maintaining the live congenic colony, homozygous mice may be bred.
- Additional Breeding and Husbandry Support
Citation
When using the B6.129S6-Trp53^tm2Xu/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #007218 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous for Trp53<tm2Xu>

Related Products and Services

Frozen Mouse Embryo	B6.129S6-Trp53<tm2Xu>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129S6-Trp53<tm2Xu>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129S6-Trp53<tm2Xu>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6.129S6-Trp53<tm2Xu>/J Frozen Embryo	$3373.50

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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Trp53tm2Xu

Allele Symbol: Trp53tm2Xu

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Trp53tm2Xu/Trp53tm2Xuinvolves: 129S6/SvEvTac

cellular phenotype

hematopoietic system phenotype

immune system phenotype

neoplasm

References

Additional - Trp53tm2Xu related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Trp53^tm2Xu

Allele Symbol: Trp53^tm2Xu

Genotype: Trp53^tm2Xu/Trp53^tm2Xu
involves: 129S6/SvEvTac

Additional - Trp53^tm2Xu related