Overview

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.

Donating Investigator

Dr. Tyler Jacks, Massachusetts Institute of Technology

Genetic overview

Genetic Background	Generation

Trp53^tm1Tyj

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Trp53	transformation related protein 53

Nf1^tm1Tyj

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Nf1	neurofibromin 1

View Genetics

Research Applications

Cancer Research
Mouse/Human Gene Homologs
Research Tools
Developmental Biology Research
Apoptosis Research
Immunology, Inflammation and Autoimmunity Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

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.

Development

These mice carry two independently-created targeted mutations, Trp53^tm1Tjy and Nf1^tm1Tyj, 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.

Selected References

Reilly KM; Loisel DA; Bronson RT; McLaughlin ME; Jacks T. 2000. Nf1;Trp53 mutant mice develop glioblastoma with evidence of strain-specific effects Nat Genet 26(1):109-13PubMed: 10973261 MGI: J:64364

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Genetics

Trp53^tm1Tyj

Allele Symbol: Trp53^tm1Tyj

Allele Name	targeted mutation 1, Tyler Jacks
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	p53-; p53^delta; p53^null; p53KO; Trp53-; Trp53^KO
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

Nf1^tm1Tyj

Allele Symbol: Nf1^tm1Tyj

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

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

neurofibromatosis

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Trp53^tm1Tyj related

Cancer Research
- Increased Tumor Incidence
  - Lymphomas
  - Other Tissues/Organs: osteosarcoma
  - Other Tissues/Organs
- Toxicology
- Tumor Suppressor Genes
Mouse/Human Gene Homologs
- Li-Fraumeni syndrome
Research Tools
- Toxicology Research
  - drug/compound testing
  - B and T cell deficiency, xenograft transplant host
Apoptosis Research
- Endogenous Regulators
Immunology, Inflammation and Autoimmunity Research
- Intracellular Signaling Molecules

Developmental Biology Research
- Embryonic Lethality (Homozygous)
Cancer Research
- Increased Tumor Incidence
  - Other Tissues/Organs
  - Other Tissues/Organs: brain
- Tumor Suppressor Genes

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Nf1^tm1Tyj/Nf1⁺ Trp53^tm1Tyj/Trp53⁺
involves: 129S2/SvPas

mammalian phenotype

nervous system phenotype
- Normal - neural crest stem cells do not abnormally persist in the peripheral nervous system in adult mice

neoplasm

increased neurofibrosarcoma incidence
- form by 6 months of age

nervous system phenotype

increased neurofibrosarcoma incidence
- form by 6 months of age

The following phenotype relates to a compound genotype created using this strain

Genotype: Nf1^tm1Tyj/Nf1⁺ Trp53^tm1Tyj/Trp53⁺
involves: 129/Sv * C57BL/6

mortality/aging

premature death
- cis-double heterozygotes die by 5 months of age and trans-double heterozygotes survive to the average age of 10 months

neoplasm

increased neurofibrosarcoma incidence
- develop in cis-double heterozygotes, usually correlated with loss of one chromosome

increased sarcoma incidence
- developed in both cis- and trans-double heterozygotes
- sarcomas in trans-double heterozygotes were similar to those found in mice with either single mutation and were usually correlated with loss of one chromosome

increased tumor incidence
- cis-double heterozygotes exhibit greater incidence of tumors than trans-double heterozygotes

nervous system phenotype

increased neurofibrosarcoma incidence
- develop in cis-double heterozygotes, usually correlated with loss of one chromosome

References

Reilly KM; Loisel DA; Bronson RT; McLaughlin ME; Jacks T. 2000. Nf1;Trp53 mutant mice develop glioblastoma with evidence of strain-specific effects Nat Genet 26(1):109-13PubMed: 10973261 MGI: J:64364

Additional - Nf1^tm1Tyj related

Additional - Trp53^tm1Tyj related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Trp53 Alternate2
- Standard PCR:Nf1
- Probe:Trp53-Probe
- Genotyping resources and troubleshooting
Breeding Considerations

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.
- Additional Breeding and Husbandry Support
Citation
When using the B6;129S2-Trp53^tm1Tyj Nf1^tm1Tyj/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008191 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or Wild-type for Trp53<tm1Tyj>, Heterozygous or Wild-type for Nf1<tm1Tyj>

Related Products and Services

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'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. 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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General Terms and Conditions

Questions about Terms of Use

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Selected References

Trp53tm1Tyj

Allele Symbol: Trp53tm1Tyj

Nf1tm1Tyj

Allele Symbol: Nf1tm1Tyj

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Trp53tm1Tyj related

Mammalian Phenotype Terms by Genotype

Genotype: Nf1tm1Tyj/Nf1+ Trp53tm1Tyj/Trp53+involves: 129S2/SvPas

mammalian phenotype

neoplasm

nervous system phenotype

Genotype: Nf1tm1Tyj/Nf1+ Trp53tm1Tyj/Trp53+involves: 129/Sv * C57BL/6

mortality/aging

neoplasm

nervous system phenotype

References

Additional - Nf1tm1Tyj related

Additional - Trp53tm1Tyj related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Trp53^tm1Tyj

Allele Symbol: Trp53^tm1Tyj

Nf1^tm1Tyj

Allele Symbol: Nf1^tm1Tyj

Genotype: Trp53^tm1Tyj related

Genotype: Nf1^tm1Tyj/Nf1⁺ Trp53^tm1Tyj/Trp53⁺
involves: 129S2/SvPas

Genotype: Nf1^tm1Tyj/Nf1⁺ Trp53^tm1Tyj/Trp53⁺
involves: 129/Sv * C57BL/6

Additional - Nf1^tm1Tyj related

Additional - Trp53^tm1Tyj related