Overview

Also Known As:Nf1/p53/Suz12

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.

Donating Investigator

Karen Cichowski, Brigham and Women's Hospital - Harvard Medical School

Genetic overview

Genetic Background	Generation

Trp53^tm1Tyj

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

Suz12^{Gt(Betageo)1Khe}

Allele Type	Gene Symbol	Gene Name
Gene trapped (Reporter, Null/Knockout)	Suz12	SUZ12 polycomb repressive complex 2 subunit

Nf1^tm1Tyj

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

View Genetics

Research Applications

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

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

View Price List

Details

Detailed Description

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).

Development

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 Trp53^tm1Tyj 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 Nf1^tm1Tyj 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 Suz12^{Gt(Betageo)1Khe}allele: 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).

Expression Data

Expressed Gene	Bgeo, fusion of beta-galactosidase and neomycin phosphotransferase genes, E. coli
Site of Expression	Embryonic stem cells.
Site of Expression	Nf1 is normally widely expressed.

Control Suggestions

101045 B6129SF2/J

Additional Information

Considerations for Choosing Controls

Selected References

De Raedt T; Beert E; Pasmant E; Luscan A; Brems H; Ortonne N; Helin K; Hornick JL; Mautner V; Kehrer-Sawatzki H; Clapp W; Bradner J; Vidaud M; Upadhyaya M; Legius E; Cichowski K. 2014. PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies. Nature 514(7521):247-51PubMed: 25119042 MGI: J:217077

View All References

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

Suz12^{Gt(Betageo)1Khe}

Allele Symbol: Suz12^{Gt(Betageo)1Khe}

Allele Name	gene trap 1, Kristian Helin
Allele Type	Gene trapped (Reporter, Null/Knockout)
Allele Synonym(s)	Suz12^-; Suz12^502gt; Suz12^Gt(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.

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

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
  - Other Tissues/Organs
  - Lymphomas
  - Other Tissues/Organs: osteosarcoma
- Toxicology
- Tumor Suppressor Genes
Immunology, Inflammation and Autoimmunity Research
- Intracellular Signaling Molecules
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

Research Tools
- Cancer Research
Cancer Research
- Tumor Suppressor Genes
- Increased Tumor Incidence
  - Other Tissues/Organs: brain
  - Cell/Tissue Type
  - Other Tissues/Organs
- Oncogenes

Mammalian Phenotype Terms by Genotype

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

Genotype: Nf1^tm1Tyj/Nf1⁺ Suz12^{Gt(Betageo)1Khe}/Suz12⁺ Trp53^tm1Tyj/Trp53⁺
involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6

mortality/aging

premature death
- mice die by 150 days

nervous system phenotype

increased glioma incidence
- 54% of mice develop high-grade gliomas
- gliomas develop on average at 3 months of age

increased neurofibrosarcoma incidence
- 38% of mice develop malignant peripheral nerve sheath tumors
- tumors develop on average at 2.3 months of age

neoplasm

increased glioma incidence
- 54% of mice develop high-grade gliomas
- gliomas develop on average at 3 months of age

increased hemangiosarcoma incidence
- 4% of develop angiosarcomas

increased histiocytic sarcoma incidence
- 62% of mice develop histiocytic sarcomas

increased lymphoma incidence
- 12% of mice develop lymphomas

increased neurofibrosarcoma incidence
- 38% of mice develop malignant peripheral nerve sheath tumors
- tumors develop on average at 2.3 months of age

increased tumor incidence

References

De Raedt T; Beert E; Pasmant E; Luscan A; Brems H; Ortonne N; Helin K; Hornick JL; Mautner V; Kehrer-Sawatzki H; Clapp W; Bradner J; Vidaud M; Upadhyaya M; Legius E; Cichowski K. 2014. PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies. Nature 514(7521):247-51PubMed: 25119042 MGI: J:217077

Additional - Nf1^tm1Tyj related

Additional - Suz12^{Gt(Betageo)1Khe} related

Additional - Trp53^tm1Tyj related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Suz12-Alternate 1
- Standard PCR:Trp53 Alternate2
- Standard PCR:Nf1
- Probe:Trp53-Probe
- Genotyping resources and troubleshooting
Breeding Considerations

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.
- Additional Breeding and Husbandry Support
Mating System
- Wildtype Trp53tm1Tyj, Wildtype Nf1tm1Tyj, Wildtype Suz12Gt(Betageo)1Khe x Heterozygous Trp53tm1Tyj, Heterozygous Nf1tm1Tyj, Heterozygous Suz12Gt(Betageo)1Khe. No reciprocal mating
Citation
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.

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 wildtype for Trp53<tm1Tyj> Nf1<tm1Tyj> Suz12<Gt(Betageo)1Khe>/Kcich

Related Products and Services

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

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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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Also Known As:Nf1/p53/Suz12

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Trp53tm1Tyj

Allele Symbol: Trp53tm1Tyj

Suz12Gt(Betageo)1Khe

Allele Symbol: Suz12Gt(Betageo)1Khe

Nf1tm1Tyj

Allele Symbol: Nf1tm1Tyj

Disease Terms

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+ Suz12Gt(Betageo)1Khe/Suz12+ Trp53tm1Tyj/Trp53+involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6

mortality/aging

nervous system phenotype

neoplasm

References

Additional - Nf1tm1Tyj related

Additional - Suz12Gt(Betageo)1Khe related

Additional - Trp53tm1Tyj related

Genotyping Protocols

Breeding Considerations

Mating System

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

Suz12^{Gt(Betageo)1Khe}

Allele Symbol: Suz12^{Gt(Betageo)1Khe}

Nf1^tm1Tyj

Allele Symbol: Nf1^tm1Tyj

Genotype: Trp53^tm1Tyj related

Genotype: Nf1^tm1Tyj/Nf1⁺ Suz12^{Gt(Betageo)1Khe}/Suz12⁺ Trp53^tm1Tyj/Trp53⁺
involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6

Additional - Nf1^tm1Tyj related

Additional - Suz12^{Gt(Betageo)1Khe} related

Additional - Trp53^tm1Tyj related