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Strain Name:

129-Trp53tm1Holl/J

Stock Number:

004301

Availability:

Repository-Cryopreserved


General Terms and Conditions

Genes & Alleles   Trp53;   Trp53tm1Holl;


Product Information

Strain Details

Type JAX® GEMM® Strain - Mutant Strain
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Targeted Mutation
Specieslaboratory mouse
Donating Investigator Monica Hollstein,   German Cancer Research Center

Strain Description
In this mutant mouse strain, the endogenous murine sequence for exons 4-9 of the targeted gene, which encode the DNA binding domain of the tumor suppressor protein, have been replaced with the homologous normal human sequence. Transcription is under the control of the endogenous mouse promoter. Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Homozygous mutant mice exhibit normal expression and functional activity of the chimeric gene. Homozygous mutant mice have normal immunodetectable levels of p53 protein accumulation in nuclei in response to UV-induced DNA damage. Thymocytes from mutant mice are as susceptible to gamma-irradiation-induced and dexamethaxone-induced apoptosis as wildtype thymocytes. This mutant mouse strain may be useful in studies related to in vivo spontaneous and induced mutation of the human TRP53 gene sequence, and pharmacological agents for altering DNA-binding activity in the human TRP53 gene.

Strain Development
A targeting vector containing sequence from exons 4-9 of the normal human gene, neomycin resistance gene and floxed (loxP site flanked) herpes simplex virus thymidine kinase gene was utilized in the construction of this mutant. The construct was electroporated into 129P2/OlaHsd derived E14.1 embryonic stem (ES) cells. Cre recombinase was transiently expressed in ES cells to remove the loxP flanked neomycin/thymidine kinase sequence. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were backcrossed to 129 mice.

Mammalian Phenotype Terms assigned by genotype

Trp53tm1Holl/Trp53tm1Holl

        involves: 129P2/OlaHsd
  • cellular phenotype
  • *normal* cellular phenotype (MGI Ref ID J:126497)
    • irradiated mouse embryonic fibroblasts do not develop chromosomal translocations

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

Trp53tm1Holl/Trp53tm1Holl

        involves: 129/Sv * 129P2/OlaHsd * C57BL/6
  • cellular phenotype
  • *normal* cellular phenotype (MGI Ref ID J:68918)
    • unlike in p53 null mice, p53 localization to UV irradiation and gamma-radiation induced apoptosis are normal
  • tumorigenesis
  • *normal* tumorigenesis (MGI Ref ID J:68918)
    • unlike in p53 null mice, no tumors develop by 8 months of age

Gene & Allele Details

Allele Symbol Trp53tm1Holl
Allele Name targeted mutation 1, Monica Hollstein
Common Name(s) HUPKI; p5372arg; p53KI; p53hki;
Mutation Made By Monica Hollstein,   German Cancer Research Center
Strain of Origin129P2/OlaHsd
ES Cell Line NameE14.1
ES Cell Line Strain129P2/OlaHsd
Gene Symbol and Name Trp53, transformation related protein 53
Chromosome 11
Gene Common Name(s) FLJ92943; LFS1; MGC112612; Tp53; p53;
Molecular Note Insertion of a loxP-flanked neomycin-thymidine kinase expression cassette replaced the mouse DNA-binding domain (exons 4-9) with the corresponding homologous segment of the normal human gene, leaving transcription under control of the endogenous promoter. Cre-mediated recombination in ES cells excised the neo-tk sequences. cDNA sequencing studies determined that transcripts from spleen of homozygous mutant mice carried the human sequence for exons 4-9, and that the gene is correctly spliced and transcribed. [MGI Ref ID J:68918]

Control Information

  Control
   000691 129X1/SvJ
 
  Considerations for Choosing Controls

Genotyping Protocols

Trp53 tm1 Holl

Colony Maintenance

Diet Information LabDiet® 5K52/5K67

Related Strains

View Strains carrying other alleles of Trp53     (12 strains)

Research Applications

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

Apoptosis Research

Cancer Research
Toxicology
Tumor Suppressor Genes

Immunology and Inflammation Research
Intracellular Signaling Molecules

Research Tools
Apoptosis Research
Toxicology Research

Trp53 related

Cancer Research
Increased Tumor Incidence (Lymphomas)
Increased Tumor Incidence (Other Tissues/Organs: osteosarcoma)

Mouse/Human Gene Homologs
Li-Fraumeni syndrome

Research Tools
Toxicology Research (B and T cell deficiency) (xenograft transplant host)
Toxicology Research (drug/compound testing)

Trp53tm1Holl related

Apoptosis Research
Endogenous Regulators

Cancer Research
Toxicology
Tumor Suppressor Genes

Immunology and Inflammation Research
Intracellular Signaling Molecules

References

Selected Reference(s)

Luo JL; Yang Q; Tong WM; Hergenhahn M; Wang ZQ; Hollstein M. 2001. Knock-in mice with a chimeric human/murine p53 gene develop normally and show wild-type p53 responses to DNA damaging agents: a new biomedical research tool. Oncogene 20(3):320-8. [PubMed: 11313961]  [MGI Ref ID J:68918]

Additional References

Price and Supply Information

Strain Name: 129-Trp53tm1Holl/J
Stock Number: 004301

Price Details

IMPORTANT NOTE: Prices are based on shipping destination. To view prices, select your shipping destination.

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Supply Details

Standard SupplyRepository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.
Supply Notes Cryorecovery - Standard.
The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services: Tel: 1-800-422-6423 or 1-207-288-5845; Email: jaxservices@jax.org.
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

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

For additional Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

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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