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| 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. | |||||||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Strain Information
Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation N3F?+1pN1
Generation DefinitionsDonating Investigator Monica Hollstein, German Cancer Research Center (DKFZ) 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-Trp53tm1Holl/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.
Control Information
| Control | ||
|---|---|---|
| 100492 B6129PF1/J | (approximate) | |
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of Trp53
004301 129-Trp53tm1Holl/J 002080 129-Trp53tm1Tyj/J 008652 129S-Trp53tm2Tyj/J 008651 129S-Trp53tm3Tyj/J 008462 B6.129P2-Trp53tm1Brn/J 002101 B6.129S2-Trp53tm1Tyj/J 008183 B6.129S4(Cg)-Trp53tm2.1Tyj/J 008182 B6.129S4-Trp53tm3.1Tyj/J 007218 B6.129S6-Trp53tm2Xu/J 011109 B6.Cg-Trp53tm2Glo/Kvm 007962 B6.FVB-Tg(MMTV-neu/OT-I/OT-II)CBnel Tg(Trp53R172H)8512Jmr/J 017767 B6;129-Trp53tm1.1Dgk/J 006980 B6;129-Trp53tm2Xu/J 008191 B6;129S2-Trp53tm1Tyj Nf1tm1Tyj/J 002103 B6;129S2-Trp53tm1Tyj/J 008181 B6;129S4-Trp53tm4Tyj/J 008361 B6;129S4-Trp53tm5Tyj/J 002526 C.129S2(B6)-Trp53tm1Tyj/J 002547 C3Ou.129S2(B6)-Trp53tm1Tyj/J 002899 FVB.129S2(B6)-Trp53tm1Tyj/J 002659 FVB/N-Tg(Trp53R172H)8512Jmr/J 002660 FVB/N-Tg(Trp53R172L)4491Jmr/J 017530 STOCK Iis2tm2(ACTB-tdTomato,-EGFP)Luo Trp53tm1Tyj Nf1tm1Par/J 012620 STOCK Trp53tm1Brd Brca1tm1Aash Tg(LGB-cre)74Acl/J 003262 STOCK Tg(Trp53A135V)L3Ber/J View Strains carrying other alleles of Trp53 (25 strains)
004301 129-Trp53tm1Holl/J
Phenotype
Phenotype Information
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Adrenocortical Carcinoma, Hereditary; ADCC (TP53)
Basal Cell Carcinoma, Susceptibility to, 7; BCC7 (TP53)
Breast Cancer (TP53)
Colorectal Cancer; CRC (TP53)
Glioma Susceptibility 1; GLM1 (TP53)
Hepatocellular Carcinoma (TP53)
Li-Fraumeni Syndrome 1; LFS1 (TP53)
Nasopharyngeal Carcinoma (TP53)
Osteogenic Sarcoma (TP53)
Pancreatic Cancer (TP53)
Papilloma of Choroid Plexus (TP53)
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Trp53tm2Holl/Trp53tm2Holl
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 (MGI Ref ID J:135505)
This mouse can be used to support research in many areas including:
Cancer Research
Toxicology
Tumor Suppressor Genes
Immunology, Inflammation and Autoimmunity Research
Intracellular Signaling Molecules
Research Tools
Apoptosis Research
Toxicology Research
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Trp53tm2Holl | ||
|---|---|---|---|
| Allele Name | targeted mutation 2, Monica Hollstein | ||
| Allele Type | Targeted (knock-in) | ||
| Common Name(s) | Trp53tm1Moho; p5372pro; | ||
| Mutation Made By | Monica Hollstein, German Cancer Research Center (DKFZ) | ||
| Strain of Origin | 129P2/OlaHsd | ||
| ES Cell Line Name | E14.1 | ||
| ES Cell Line Strain | 129P2/OlaHsd | ||
| Expressed Gene | TRP53, tumor protein p53, Human | ||
| Gene Symbol and Name | Trp53, transformation related protein 53 | ||
| Chromosome | 11 | ||
| Gene Common Name(s) | BCC7; LFS1; P53; p44; | ||
| 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. Thismutation corresponds to the prevalent allele among humans of non-Northern European descent. [MGI Ref ID J:135505] | ||
References
References provided by MGI
Selected Reference(s)
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 Ref ID J:135505]
Additional References
Trp53tm2Holl relatedFrank 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 Ref ID 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 Ref ID J:161187]
Health & husbandry
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Health & Colony Maintenance Information
Animal Health Reports
Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.Colony Maintenance
Breeding & Husbandry When maintaining a live colony, these mice can be bred as homozygotes.
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
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Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $1980.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryorecovery - Standard.
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 11 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. IMPORTANT NOTE: 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
| Pricing for International shipping destinations |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2574.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryorecovery - Standard.
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 11 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. IMPORTANT NOTE: 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
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Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Control Information
| Control | ||
|---|---|---|
| 100492 B6129PF1/J | (approximate) | |
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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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.Ordering Information
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