These mice carry Trp53 and Nf1 targeted mutations on the same homolog of chromosome 11 (in cis). These mutations are approximately 10 Mbp apart and may segregate independently of one another. Double heterozygotes survive an average of five months and exhibit a significant increase in the percentage of soft tissue sarcomas. About 30% of tumors from the Nf1/Trp53 cis animals stain positively for S100 (consistent with glial cell origin) and exhibit classic histological features of malignant peripheral nerve sheath tumors (MPNSTs). This strain may be useful in studies of astrocytomas/glioblastomas and tumor suppressor genes.
Dr. Tyler Jacks, Massachusetts Institute of Technology
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Trp53 | transformation related protein 53 |
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Nf1 | neurofibromin 1 |
These mice carry Trp53 and Nf1 targeted mutations (in cis) on chromosome 11. These mutations are approximately 10 Mbp apart and may segregate independently of one another. Double homozygotes are embryonic lethal. Double heterozygotes survive an average of five months and exhibit a significant increase in the percentage of soft tissue sarcomas compared with mice of other genotypes (Nf1 +/-, 5%; p53, 57%; Nf1/Trp53 trans, 36%; Nf1/Trp53 cis, 81%). Furthermore, although Nf1/Trp53 trans mice exclusively develop osteo-, fibro-, rhabdomyo-, and hemangiosarcomas, about 30% of tumors from the Nf1/Trp53 cis animals stain positively for S100 (consistent with glial cell origin) and exhibit classic histological features of malignant peripheral nerve sheath tumors (MPNSTs). This strain may be useful in studies of astrocytomas/glioblastomas and tumor suppressor genes.
These mice carry two independently-created targeted mutations, Trp53tm1Tjy and Nf1tm1Tyj, that are approximately 10 Mbp apart on the same homolog of chromosome 11 (in cis). To create the Trp53 mutation, a targeting vector was designed to replace approximately 40% of the coding sequences (involving exons 2-6) with a neomycin resistance cassette. To create the Nf1 mutation, a targeting vector was designed to insert a neomycin resistance cassette and delete the first 42 codons of exon 31, the exon 31 splice acceptor site, and approximately 2 kb of intron 30. Each of the targeting vectors was independently electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Independent strains carrying germline mutations in Trp53 and Nf1 were generated on a mixed 129S2/SvPas and C57BL/6 genetic background, and then then intercrossed. Mice that underwent meiotic recombination events placing both mutations on the same homolog of chromosome 11 (in cis) were selected. This double mutant strain was maintained on a mixed 129S2/SvPas and C57BL/6 genetic background by the donating laboratory prior to sending to The Jackson Laboratory Repository. Upon arrival, males that were heterozygous for both mutations were identified and used to cryopreserve sperm.
Allele Name | targeted mutation 1, Tyler Jacks |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | p53-; p53delta; p53null; p53KO; Trp53-; Trp53KO |
Gene Symbol and Name | Trp53, transformation related protein 53 |
Gene Synonym(s) | |
Site of Expression | Normal Trp53 expression is widespread. |
Strain of Origin | 129S2/SvPas |
Chromosome | 11 |
General Note | This mutant allele was produced by a targeted neo insertion into the Trp53 locus. Homozygotes show no visible phenotype but develop tumors at 3-6 months of age. Heterozygotes develop tumors at 10 months of age. These mice model some of the features of human Li-Fraumeni syndrome (OMIM 151623), a form of familial breast cancer with mutations in TRP53 (J:16022)(J:16023) A specific human mutation found in hepatocellular carcinomas caused by hepatitis B infection or by aflatoxin exposure has been created in a mouse model, resulting in a similar gene product (J:27363). |
Molecular Note | A neomycin cassette replaced 40% of the coding sequences beginning with exon 2 (upstream of the translation start site) and extending into exon 6. |
Mutations Made By | Dr. Tyler Jacks, Massachusetts Institute of Technology |
Allele Name | targeted mutation 1, Tyler Jacks |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Nf1-; Nf1n31 |
Gene Symbol and Name | Nf1, neurofibromin 1 |
Gene Synonym(s) | |
Site of Expression | Nf1 is normally widely expressed. |
Strain of Origin | 129S2/SvPas |
Chromosome | 11 |
Molecular Note | A neomycin resistance cassette replaced the first 42 codons of exon 31, the exon 31 splice acceptor site, and approximately 2 kb of intron 30. This allele is a null allele; no stable full-length protein is made. |
Mutations Made By | Dr. Tyler Jacks, Massachusetts Institute of Technology |
These mice carry Trp53 and Nf1 targeted mutations approximately 10 Mbp apart on the same homolog of chromosome 11 (in cis). When maintained as a live colony, double heterozygotes may be bred. Heterozygotes have shortened lifespans (~5 months) due to tumor formation, however. Double homozygotes are embryonic lethal. If breeding double mutant mice to wildtype mice, the resulting offspring may be segregating for each mutation.
When using the B6;129S2-Trp53tm1Tyj Nf1tm1Tyj/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008191 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or Wild-type for Trp53<tm1Tyj>, Heterozygous or Wild-type for Nf1<tm1Tyj> |
Frozen Mouse Embryo | B6;129S2-Trp53<tm1Tyj> Nf1<tm1Tyj>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6;129S2-Trp53<tm1Tyj> Nf1<tm1Tyj>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6;129S2-Trp53<tm1Tyj> Nf1<tm1Tyj>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | B6;129S2-Trp53<tm1Tyj> Nf1<tm1Tyj>/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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