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.
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 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.
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.
Expressed Gene | TRP53, tumor protein p53, Human |
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Site of Expression |
Allele Name | targeted mutation 2, Monica Hollstein |
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Allele Type | Targeted (Humanized sequence) |
Allele Synonym(s) | p5372pro; Trp53tm1Moho |
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 | 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) |
When maintaining a live colony, these mice can be bred as homozygotes.
When using the B6;129-Trp53tm2Holl/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008045 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous for Trp53<tm2Holl> |
Frozen Mouse Embryo | B6;129-Trp53<tm2Holl>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6;129-Trp53<tm2Holl>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6;129-Trp53<tm2Holl>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | B6;129-Trp53<tm2Holl>/J Frozen Embryo | $3373.50 |
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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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