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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
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Homozygote (Female x Male) 26-JAN-08 Species laboratory mouse Generation N3F?+F3 (31-DEC-08) Donating 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 007962 B6.FVB-Tg(MMTV-neu/OT-I/OT-II)CBnel Tg(Trp53R172H)8512Jmr/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 003262 STOCK Tg(Trp53A135V)L3Ber/J View Strains carrying other alleles of Trp53 (21 strains)
Phenotype
Phenotype Information
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 (MGI Ref ID J:135505)
- mouse embryonic fibroblasts (MEFs) generated from embryos immortalize at the same rate as wild-type MEFs
This mouse can be used to support research in many areas including:
Trp53 relatedApoptosis Research
Cancer Research
Toxicology
Tumor Suppressor Genes
Immunology and Inflammation Research
Intracellular Signaling Molecules
Research Tools
Apoptosis Research
Toxicology Research
Apoptosis Research
Endogenous Regulators
Cancer Research
Increased Tumor Incidence
Lymphomas
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
drug/compound testing
Genes & Alleles
Gene & Allele Information
| 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 | ||
| Gene Symbol and Name | Trp53, transformation related protein 53 | ||
| Chromosome | 11 | ||
| Gene Common Name(s) | FLJ92943; LFS1; MGC112612; p53; | ||
| 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] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Trp53tm2Holl, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References
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]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX12
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, these mice can be bred as homozygotes. Mating System Homozygote x Homozygote (Female x Male) 26-JAN-08 Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $209.90 Female or Male Homozygous for Trp53tm2Holl
Pairs /Price (US dollars $) Pair Genotype $419.80 Homozygous for Trp53tm2Holl x Homozygous for Trp53tm2Holl
Additional Supply Details
| Pricing for International shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $272.90 Female or Male Homozygous for Trp53tm2Holl
Pairs /Price (US dollars $) Pair Genotype $545.80 Homozygous for Trp53tm2Holl x Homozygous for Trp53tm2Holl
Additional Supply Details
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Supply Details
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of approximately nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within two business days following order placement. |
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| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| 100492 B6129PF1/J | (approximate) | |
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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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.Ordering and Purchasing Information
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Terms of Use
Terms of Use
General Terms and Conditions
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:
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Contact information
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| fax: | 207-288-6655 |
JAX® Mice, Products & Services Conditions of Use
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