Strain Name:

B6;129S2-Nf2tm1Tyj/J

Stock Number:

008190

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Availability:

Cryopreserved - Ready for recovery

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Most embryos that are homozygous for this targeted mutation fail between embryonic days 6.5 and 7.0. Heterozygotes develop a variety of malignant tumors over the course of 10-30 months, including osteosarcoma (63%), lymphoma (15%), lung adenocarcinoma (10%), hepatocellular carcinoma (9%), and fibrosarcoma (9%). This strain may be useful in studies of embryonic development and cancer.

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Specieslaboratory mouse
GenerationN1p
Generation Definitions
 
Donating InvestigatorDr. Tyler Jacks,   Massachusetts Institute of Technology

Description
Most embryos that are homozygous for this targeted mutation fail between embryonic days 6.5 and 7.0, exhibiting a collapsed extraembryonic region and the absence of organized extraembryonic ectoderm. The embryo proper continues to develop, but fails to initiate gastrulation. Heterozygotes develop a variety of malignant tumors over the course of 10-30 months, including osteosarcoma (63%), lymphoma (15%), lung adenocarcinoma (10%), hepatocellular carcinoma (9%), and fibrosarcoma (9%). A high rate of metastasis to distant sites such as the lung and liver was found. Schwannomas, meningiomas and ependymomas were not detected. RT-PCR analysis and sequencing of the product have shown that a mutant form of mRNA is transcribed and spliced. Immunoblotting fails to detect any full-length or shortened protein products, however. This strain may be useful in studies of embryonic development and cancer.

Development
A targeting vector was designed to replace the 3' half of exon 2, all of exon 3, and the intervening intronic sequences with a neomycin resistance gene in opposite orientation. The targeting vector was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Resultant chimeric animals were crossed with C57BL/6. The strain was been maintained on a mixed 129S2/SvPas and C57BL/6 mixed background by the donating laboratory.

Control Information

  Control
   Wild-type from the colony
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- No similarity to the expected human disease phenotype was found. One or more human genes are associated with this human disease. The mouse genotype may involve mutations to orthologs of one or more of these genes, but the phenotype did not resemble the disease.
Meningioma, Familial, Susceptibility to
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Neurofibromatosis, Type II; NF2   (NF2)
Schwannomatosis 1; SWNTS1   (NF2)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Nf2tm1Tyj/Nf2+

        either: (involves: 129S2/SvPas * 129S4/SvJae * C57BL/6) or (involves: 129S2/SvPas * C57BL/6J)
  • tumorigenesis
  • *normal* tumorigenesis
    • schwannomas, meningiomas, or ependymomas were not detected   (MGI Ref ID J:47282)
    • increased lymphoma incidence   (MGI Ref ID J:47282)
    • increased malignant tumor incidence
      • increased incidence of highly metastatic tumors, including osteosarcoma, lymphoma, lung adenocarcinomas, hepatocellular carcinoma and fibrosarcoma   (MGI Ref ID J:47282)
      • osteosarcoma frequency was higher in females and the frequency of fibrosarcomas was higher in males   (MGI Ref ID J:47282)
      • increased carcinoma incidence   (MGI Ref ID J:47282)
        • increased lung adenocarcinoma incidence   (MGI Ref ID J:47282)
      • increased sarcoma incidence   (MGI Ref ID J:47282)
        • increased fibrosarcoma incidence   (MGI Ref ID J:47282)
        • increased osteosarcoma incidence   (MGI Ref ID J:47282)

Nf2tm1Tyj/Nf2tm1Tyj

        involves: 129S2/SvPas * C57BL/6J
  • mortality/aging
  • partial embryonic lethality between implantation and somite formation
    • most die between E7.5 and E8.5; underdeveloped structures observed at E6.5   (MGI Ref ID J:40596)
  • embryogenesis phenotype
  • abnormal developmental patterning   (MGI Ref ID J:40596)
    • abnormal dorsal-ventral axis patterning
      • abnormal morphology of the visceral endoderm is suggestive of a defect in the establishment of the primary dorsal-ventral axis   (MGI Ref ID J:40596)
    • absent mesoderm
      • mesoderm does not form due to failure of gastrulation   (MGI Ref ID J:40596)
    • failure to gastrulate
      • gastrulation is not initiated   (MGI Ref ID J:40596)
  • abnormal embryonic tissue morphology   (MGI Ref ID J:40596)
    • absent mesoderm
      • mesoderm does not form due to failure of gastrulation   (MGI Ref ID J:40596)
  • abnormal extraembryonic tissue morphology   (MGI Ref ID J:40596)
    • abnormal placenta morphology   (MGI Ref ID J:40596)
      • small ectoplacental cone   (MGI Ref ID J:40596)
    • absent extraembryonic ectoderm   (MGI Ref ID J:40596)
    • disorganized extraembryonic tissue   (MGI Ref ID J:40596)
  • abnormal visceral endoderm morphology
    • abnormal visceral endoderm; more than one region of squamous morphology is often seen suggesting a defect in the establishment of the primary embryonic axis   (MGI Ref ID J:40596)
View Research Applications

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

Cancer Research
Increased Tumor Incidence
      Adenomas
      Adenomas: lung
      Hepatomas
      Hepatomas: hepatacellular carcinoma
      Lymphomas
      Other Tissues/Organs
      Other Tissues/Organs: osteosarcoma

Developmental Biology Research
Embryonic Lethality (Homozygous)

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Nf2tm1Tyj
Allele Name targeted mutation 1, Tyler Jacks
Allele Type Targeted (Null/Knockout)
Common Name(s) Merlin-; Nf2-; Nf2KO2-3;
Mutation Made ByDr. Tyler Jacks,   Massachusetts Institute of Technology
Strain of Origin129S2/SvPas
ES Cell Line NameD3
ES Cell Line Strain129S2/SvPas
Gene Symbol and Name Nf2, neurofibromatosis 2
Chromosome 11
Gene Common Name(s) ACN; BANF; SCH; merlin; moesin-ezrin-radixin-like protein; schwannomin;
Molecular Note The 3' half of exon 2, all of exon 3 and intervening sequences were replaced by a neomycin cassette inserted in the reverse transcriptional orientation to the gene. RT-PCR analysis demonstrated that an aberrant transcript was expressed from this allele that spliced exon 1 to exon 5. However, immunoblot analysis on extracts derived from homozygous ES cells demonstrated that no stable mutant protein was detectable. [MGI Ref ID J:40596]

Genotyping

Genotyping Information

Genotyping Protocols

Nf2tm1Tyj, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

McClatchey AI; Saotome I; Ramesh V; Gusella JF; Jacks T. 1997. The Nf2 tumor suppressor gene product is essential for extraembryonic development immediately prior to gastrulation. Genes Dev 11(10):1253-65. [PubMed: 9171370]  [MGI Ref ID J:40596]

Additional References

Nf2tm1Tyj related

Altomare DA; Vaslet CA; Skele KL; De Rienzo A; Devarajan K; Jhanwar SC; McClatchey AI; Kane AB; Testa JR. 2005. A mouse model recapitulating molecular features of human mesothelioma. Cancer Res 65(18):8090-5. [PubMed: 16166281]  [MGI Ref ID J:101723]

Li W; Cooper J; Karajannis MA; Giancotti FG. 2012. Merlin: a tumour suppressor with functions at the cell cortex and in the nucleus. EMBO Rep 13(3):204-15. [PubMed: 22482125]  [MGI Ref ID J:186214]

McClatchey AI; Saotome I; Mercer K; Crowley D; Gusella JF; Bronson RT; Jacks T. 1998. Mice heterozygous for a mutation at the Nf2 tumor suppressor locus develop a range of highly metastatic tumors. Genes Dev 12(8):1121-33. [PubMed: 9553042]  [MGI Ref ID J:47282]

Weiss WA; Israel M; Cobbs C; Holland E; James CD; Louis DN; Marks C; McClatchey AI; Roberts T; Van Dyke T; Wetmore C; Chiu IM; Giovannini M; Guha A; Higgins RJ; Marino S; Radovanovic I; Reilly K; Aldape K. 2002. Neuropathology of genetically engineered mice: consensus report and recommendations from an international forum. Oncogene 21(49):7453-63. [PubMed: 12386807]  [MGI Ref ID J:79667]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & HusbandryWhen maintained as a live colony, heterozygotes may be bred.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2525.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3283.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   Wild-type from the colony
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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.
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