These Trp53 knock-in mice carry the human sequence of the DNA binding domain of the tumor suppressor protein and exhibit normal expression and functional activity of the chimeric gene.
Monica Hollstein, German Cancer Research Center (DKFZ)
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Humanized sequence) | Trp53 | transformation related protein 53 |
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.
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.
Expressed Gene | TRP53, tumor protein p53, Human |
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Site of Expression |
Allele Name | targeted mutation 1, Monica Hollstein |
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Allele Type | Targeted (Humanized sequence) |
Allele Synonym(s) | HUPKI; p5372arg; p53hki; p53KI |
Gene Symbol and Name | Trp53, transformation related protein 53 |
Gene Synonym(s) | |
Expressed Gene | TRP53, tumor protein p53, Human |
Strain of Origin | 129P2/OlaHsd |
Chromosome | 11 |
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. |
Mutations Made By | Monica Hollstein, German Cancer Research Center (DKFZ) |
When using the Hupki mouse strain in a publication, please cite the originating article(s) and include JAX stock #004301 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Homozygous for Trp53<tm1Holl>, 1 pair minimum |
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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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