JAX Mouse Strain Datasheet - 008045

B6;129-Trp53^tm2Holl/J

Stock No:: 008045

Targeted Mutation

Cryo Recovery

Overview

In this mutant strain, the sequence of the endogenous mouse gene (exons 4-9) has been replaced with the homologous human TRP53 region including sequence encoding proline at codon 72 (human polymorphic site). Immortalized cell lines derived from primary embryonic fibroblasts harvested from these mice frequently harbor a TRP53 (p53) mutation in the DNA binding domain typical of those found in human tumors. This mutant mouse strain may be useful in studies related to spontaneous and induced mutation of the human TRP53 gene in human cancers, and for testing pharmacological agents in vivo for their activity in altering DNA-binding activity of mutant TRP53 proteins found in tumors.

Donating Investigator

Monica Hollstein, German Cancer Research Center (DKFZ)

Genetic overview

Genetic Background	Generation

Trp53^tm2Holl

Allele Type	Gene Symbol	Gene Name
Targeted (Humanized sequence)	Trp53	transformation related protein 53

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Research Applications

Apoptosis Research
Cancer Research
Immunology, Inflammation and Autoimmunity Research
Research Tools

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Base Price

Starting at:

$2,595.00 Domestic price Cryo Recovery

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Details

Detailed Description

In this mutant strain, exons 4-9 of the endogenous mouse Trp53 gene have been replaced with the homologous human TRP53 region. Transcription of the human sequence is under the control of the endogenous mouse promoter. The inserted human sequence segment encodes the DNA binding domain and the TRP53 polyproline domain. This latter domain contains a polymorphism at codon 72 that encodes either arginine or proline in human populations. This mutant strain expresses the proline variant at codon 72 and the related strain, 129-Trp53^tm1Holl/J (Stock No. 004301) expresses the arginine variant. Mice that are homozygous for this mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Immortalized cell lines derived from primary embryonic fibroblasts harvested from these mice frequently harbor a TRP53 (p53) mutation in the DNA binding domain typical of those found in human tumors. This mutant mouse strain may be useful in studies related to spontaneous and induced mutation of the human TRP53 gene in human cancers, and for testing pharmacological agents in vivo for their activity in altering DNA-binding activity of mutant TRP53 proteins found in tumors.

Development

A targeting vector containing sequence from exons 4-9 of the human TRP53 gene encoding proline at codon 72 (human polymorphic site) and a floxed (loxP site flanked) PGKneo cassette were utilized in the construction of this mutant. The construct was electroporated into 129P2/OlaHsd derived E14.1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts, and the resulting chimeric animals were crossed to C57BL/6. Offspring with germline transmission of the human TRP53 sequences were crossed with a Cre recombinase-expressing strain (on a C57BL/6J background) to remove the floxed PGKneo cassette, and then backcrossed to 129 mice for 3 generations.

Expression Data

Expressed Gene	TRP53, tumor protein p53, Human
Site of Expression

Control Suggestions

Approximate Controls

100492 B6129PF1/J

Additional Information

Considerations for Choosing Controls

Selected References

Reinbold M; Luo JL; Nedelko T; Jerchow B; Murphy ME; Whibley C; Wei Q; Hollstein M. 2008. Common tumour p53 mutations in immortalized cells from Hupki mice heterozygous at codon 72. Oncogene 27(19):2788-94. PubMed: 17998932 MGI: J:135505

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Genetics

Trp53^tm2Holl

Allele Symbol: Trp53^tm2Holl

Allele Name	targeted mutation 2, Monica Hollstein
Allele Type	Targeted (Humanized sequence)
Allele Synonym(s)	Trp53^tm1Moho; p53^72pro
Gene Symbol and Name	Trp53, transformation related protein 53
Gene Synonym(s)	BCC7; LFS1; P53; TRP53; p44; p53
Expressed Gene	TRP53, tumor protein p53, Human
Strain of Origin	129P2/OlaHsd
Chromosome	11
Molecular Note	Exons 4 through 9 were replaced with corresponding exons from the human gene with a sequence variant in exon 4 that results in a proline at amino acid position 72. A floxed neo cassette used for selection was removed by cre mediated recombination. This mutation corresponds to the prevalent allele among humans of non-Northern European descent.
Mutations Made By	Monica Hollstein, German Cancer Research Center (DKFZ)

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Apoptosis Research
Cancer Research
- Toxicology
- Tumor Suppressor Genes
Immunology, Inflammation and Autoimmunity Research
- Intracellular Signaling Molecules
Research Tools
- Apoptosis Research
- Toxicology Research

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^tm2Holl/Trp53^tm2Holl
involves: 129P2/OlaHsd

normal phenotype

no abnormal phenotype detected
- mouse embryonic fibroblasts (MEFs) generated from embryos immortalize at the same rate as wild-type MEFs

References

Reinbold M; Luo JL; Nedelko T; Jerchow B; Murphy ME; Whibley C; Wei Q; Hollstein M. 2008. Common tumour p53 mutations in immortalized cells from Hupki mice heterozygous at codon 72. Oncogene 27(19):2788-94. PubMed: 17998932 MGI: J:135505

Additional - Trp53^tm2Holl related

Frank AK; Leu JI; Zhou Y; Devarajan K; Nedelko T; Klein-Szanto A; Hollstein M; Murphy ME. 2011. The codon 72 polymorphism of p53 regulates interaction with NF-{kappa}B and transactivation of genes involved in immunity and inflammation. Mol Cell Biol 31(6):1201-13. PubMed: 21245379 MGI: J:170615
Whibley C; Odell AF; Nedelko T; Balaburski G; Murphy M; Liu Z; Stevens L; Walker JH; Routledge M; Hollstein M. 2010. Wild-type and Hupki (human p53 knock-in) murine embryonic fibroblasts: p53/ARF pathway disruption in spontaneous escape from senescence. J Biol Chem 285(15):11326-35. PubMed: 20118236 MGI: J:161187

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous for Trp53<tm2Holl>

Progeny testing is not required

The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. 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. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 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.

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.

Payment Terms and Conditions

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.

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.

Terms Of Use

Terms of Use

General Terms and Conditions

Questions about Terms of Use

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Licensing Information

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The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Selected References

Trp53tm2Holl

Allele Symbol: Trp53tm2Holl

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Trp53tm2Holl/Trp53tm2Hollinvolves: 129P2/OlaHsd

normal phenotype

References

Additional - Trp53tm2Holl 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

Progeny testing is not required

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^tm2Holl

Allele Symbol: Trp53^tm2Holl

Genotype: Trp53^tm2Holl/Trp53^tm2Holl
involves: 129P2/OlaHsd

Additional - Trp53^tm2Holl related