These NPS+/- mice carry Trp53, Nf1, and Suz12 mutations on chromosome 11 (in cis) and develop high-grade gliomas and malignant peripheral nerve sheath tumors by approximately 3.5 months. They are suitable for use in applications related to the study of neurofibromatosis type 1 and tumor suppressor genes.
Karen Cichowski, Brigham and Women's Hospital - Harvard Medical School
Genetic Background | Generation |
---|---|
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Trp53 | transformation related protein 53 |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Nf1 | neurofibromin 1 |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Gene trapped (Reporter, Null/Knockout) | Suz12 | SUZ12 polycomb repressive complex 2 subunit |
These NPS+/- mice carry Trp53, Nf1, and Suz12 mutations on chromosome 11 (in cis), which is similar to conditions found in some human neurofibromatosis type 1 patients. Triple homozygotes are embryonic lethal. By 3 months of age, more than half (54%) of mice heterozygous for all 3 alleles, in cis, develop high-grade gliomas. Triple heterozygotes develop malignant peripheral nerve sheath tumors by 3.5 months of age, develop histiocytic sarcoma, lymphoma, and angiosarcoma, and have a shortened lifespan (approximately 5 months).
This triple mutant line was generated by intercrossing the single mutant lines to obtain triple heterozygotes with all 3 alleles in cis on chromosome 11. Mice that underwent meiotic recombination events placing all 3 mutations on the same homolog of chromosome 11 (in cis) were selected.
For the Trp53tm1Tyj allele: a targeting vector was designed to replace approximately 40% of the coding sequences (involving exons 2-6) with a neomycin resistance cassette. The construct was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice. It is not known if the mice were backcrossed to C57BL/6 mice. The Donating Investigator obtained the mice from The Jackson Laboratory.
For the Nf1tm1Tyj allele: a targeting vector was use to replace the first 42 codons of exon 31, the exon 31 splice acceptor site, and approximately 2 kb of intron 30 with a neomycin resistance cassette (oriented in an opposite transcriptional direction). The vector was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were tested for germline transmission. This strain was obtained by the Donating Investigator from Dr. Tyler Jacks. The mice were backcrossed to C57BL/6 background more than twelve times by the donating laboratory.
For the Suz12Gt(Betageo)1Kheallele: gene trap vector containing β-GEO
was inserted into intron 7, generating a truncation product of 276 N-terminal SUZ12 amino acids fused to 1323 amino acids of the β-GEO (beta-galactosidase-neomycin) protein. The vector was electroporated into unspecified 129P2/OlaHsd derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric male animals were crossed to C57BL/6 mice. It is not known if the mice were backcrossed to C57BL/6 mice. The Donating Investigator obtained the mice from Dr. Kristian Helin.
Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).
Expressed Gene | Bgeo, fusion of beta-galactosidase and neomycin phosphotransferase genes, E. coli |
---|---|
Site of Expression | Embryonic stem cells. |
Allele Name | targeted mutation 1, Tyler Jacks |
---|---|
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 |
---|---|
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 |
Allele Name | gene trap 1, Kristian Helin |
---|---|
Allele Type | Gene trapped (Reporter, Null/Knockout) |
Allele Synonym(s) | Suz12-; Suz12502gt; Suz12Gt(XG122)Byg |
Gene Symbol and Name | Suz12, SUZ12 polycomb repressive complex 2 subunit |
Gene Synonym(s) | |
Expressed Gene | Bgeo, fusion of beta-galactosidase and neomycin phosphotransferase genes, E. coli |
Site of Expression | Embryonic stem cells. |
Strain of Origin | 129P2/OlaHsd |
Chromosome | 11 |
Molecular Note | A gene trap vector inserted into intron 7 which created a truncation containing 276 N-terminal amino acids fused to 1323 amino acids of the Betagalactosidase-neo protein. The translated protein was functionally inactive. |
These mice carry Trp53, Nf1, and Suz12 mutations on chromosome 11 (in cis). When maintained as a live colony, triple heterozygotes may be bred. Heterozygotes have shortened lifespans (approximately 5 months) due to tumor formation, however. Triple homozygotes are embryonic lethal. If breeding triple mutant mice to wildtype mice, the resulting offspring may be segregating for each mutation.
When using the Nf1/p53/Suz12 mouse strain in a publication, please cite the originating article(s) and include JAX stock #027678 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Trp53<tm1Tyj> Nf1<tm1Tyj> Suz12<Gt(Betageo)1Khe>/Kcich |
Frozen Mouse Embryo | B6;129-Trp53<tm1Tyj> Nf1<tm1Tyj> Suz12<Gt(Betageo)1Khe>/Kcic | $2595.00 |
Frozen Mouse Embryo | B6;129-Trp53<tm1Tyj> Nf1<tm1Tyj> Suz12<Gt(Betageo)1Khe>/Kcic | $2595.00 |
Frozen Mouse Embryo | B6;129-Trp53<tm1Tyj> Nf1<tm1Tyj> Suz12<Gt(Betageo)1Khe>/Kcic | $3373.50 |
Frozen Mouse Embryo | B6;129-Trp53<tm1Tyj> Nf1<tm1Tyj> Suz12<Gt(Betageo)1Khe>/Kcic | $3373.50 |
Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.
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.
What information were you hoping to find through your search?
How easy was it to find what you were looking for?
We may wish to follow up with you. Enter your email if you are happy for us to connect and reachout to you with more questions.
Please Enter a Valid Email Address
Thank you for sharing your feedback! We are working on improving the JAX Mice search. Come back soon for exciting changes.