Strain Name:

129S.B6-Tg(KRT14-Esr1/HRAS)1Pkha/J

Stock Number:

006403

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Availability:

Cryopreserved - Ready for recovery

Use Restrictions Apply, see Terms of Use

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 Congenic; Mutant Strain; Transgenic;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
GenerationN6pN1
Generation Definitions
 
Donating Investigator Paul Khavari,   Stanford University

Description
Mice hemizygous for this "K14-ER:Ras" transgene are viable and fertile, with expression of the ER:Ras fusion protein (constitutively active G12V mutant form of the catalytic domain of human H-ras (H-rasV12) fused at its amino terminal with the G525R mutant murine estrogen receptor ligand binding domain (ERTM)) directed to epidermis by the human keratin 14 promoter. Because of the ERTM region of the fusion protein, ER:Ras is restricted to the cytoplasm and the biochemical activity of the ER:Ras fusion gene can be induced following tamoxifen administration. For example, prolonged (4 weeks) induction of human H-RasG12V activity promotes the undifferentiated, proliferative phenotypic characteristics observed in epidermal cancer; including hyperplasia, increased mitotic index, decreased expression of differentiation markers and increased expression of beta-1 and beta-4 integrin subunits. H-RasG12V-induced skin abnormalities were entirely reversed within one month after 4OHT cessation. These mice have a similar 4OHT-inducible skin phenotype as the transgenic mice expressing human Raf-1[DD] (Stock No. 006661) or human Mek1R4F (Stock No. 006822), and may be useful in studies of the Ras/Raf/MEK/ERK cell proliferation and differentiation pathway, as well as to elucidate cellular events preceding skin cancer cell transformation.

The G525R mutant murine estrogen receptor ligand binding domain (ERTM) does not bind its natural ligand (17β-estradiol) at physiological concentrations; but will bind the synthetic estrogen receptor ligands 4-hydroxytamoxifen (OHT or tamoxifen) and, with lesser sensitivity, ICI 182780. Restricted to the cytoplasm, ERTM fusion proteins can only gain access to the nuclear compartment after exposure to tamoxifen. To counteract the mixed estrogen agonist effects of tamoxifen injections, which can result in late fetal abortions in pregnant mice, progesterone may be coadministered.

Development
The K14-ER:Ras transgene was designed with a 2075-bp human keratin 14 promoter sequence upstream of the constitutively active G12V mutant form of the catalytic domain of human H-ras (H-rasV12) fused at its amino terminal with the G525R mutant murine estrogen receptor ligand binding domain (ERTM), which renders transgene expression tamoxifen (4OHT) inducible yet estrogen insensitive. This transgene was injected into the pronuclei of C57BL/6 embryos and chimeric founders were established. Mice were then backcrossed to "129/SvEv" mice for 5 generations prior to arrival at The Jackson Laboratory.

Control Information

  Control
   Noncarrier
   002448 129S1/SvImJ (approximate)
 
  Considerations for Choosing Controls

Related Strains

View Strains carrying other alleles of HRAS     (3 strains)

View Strains carrying other alleles of KRT14     (13 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on transgenic expression of an ortholog of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested.
Bladder Cancer   (HRAS)
Costello Syndrome; CSTLO   (HRAS)
Nevus, Epidermal   (HRAS)
Schimmelpenning-Feuerstein-Mims Syndrome; SFM   (HRAS)
Thyroid Carcinoma, Follicular; FTC   (HRAS)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

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

Tg(KRT14-Esr1/HRAS)1Pkha/0

        involves: C57BL/6
  • integument phenotype
  • hyperkeratosis
    • with continuous 4-hydroxy-testosterone (4OHT) application, hyperkeratosis is observed after 3 weeks, increasing in severity with transgene expression level   (MGI Ref ID J:81660)
  • thick skin
    • with continuous 4-hydroxy-testosterone (4OHT) application, skin thickening is observed after 3 weeks, increasing in severity with transgene expression level   (MGI Ref ID J:81660)
View Research Applications

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

Cancer Research
Genes Regulating Growth and Proliferation
Increased Tumor Incidence
      Skin Cancers
      Skin Cancers: Induced
Other

Cell Biology Research
Genes Regulating Growth and Proliferation
Signal Transduction

Dermatology Research
Other

Research Tools
Cancer Research
Cell Biology Research
Dermatology Research

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Tg(KRT14-Esr1/HRAS)1Pkha
Allele Name transgene insertion 1, Paul A Khavari
Allele Type Transgenic (Constitutively active, Inducible, Inserted expressed sequence)
Common Name(s) K14-ER:Ras;
Mutation Made By Paul Khavari,   Stanford University
Strain of OriginC57BL/6
Expressed Gene HRAS, Harvey rat sarcoma viral oncogene homolog, human
Promoter KRT14, keratin 14, human
General Note Multiple mouse lines were generated, with varying transgene copy numbers and expression levels of the fusion protein. Lines were identified only as H, M, and L for high, medium and low copy number, respectively.
Molecular Note The transgene contains a 2075-bp human keratin 14 promoter construct driving expression of a cDNA that encodes a fusion protein comprising a constitutively active mutant form of the catalytic domain of human HRAS, in which glycine at amino acid position12 is replaced by arginine (G12V), joined at its amino terminal to a mutant mouse estrogen receptor ligand-binding domain in which replacement of glycine by arginine at amino acid position 525 (G525R, "ERTM") renders the fusion protein's activity inducible by 4-hydroxytamoxifen, but unresponsive to natural estrogen (17beta-estradiol). [MGI Ref ID J:118583] [MGI Ref ID J:118586] [MGI Ref ID J:118587] [MGI Ref ID J:55801] [MGI Ref ID J:81660]
 
 

Genotyping

Genotyping Information

Genotyping Protocols

Tg(KRT14-Esr1/HRAS)1Pkha, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Tg(KRT14-Esr1/HRAS)1Pkha related

Dajee M; Tarutani M; Deng H; Cai T; Khavari PA. 2002. Epidermal Ras blockade demonstrates spatially localized Ras promotion of proliferation and inhibition of differentiation. Oncogene 21(10):1527-38. [PubMed: 11896581]  [MGI Ref ID J:118583]

Ewing SJ; Zhu S; Zhu F; House JS; Smart RC. 2008. C/EBPbeta represses p53 to promote cell survival downstream of DNA damage independent of oncogenic Ras and p19(Arf). Cell Death Differ 15(11):1734-44. [PubMed: 18636078]  [MGI Ref ID J:154352]

Jameson KL; Mazur PK; Zehnder AM; Zhang J; Zarnegar B; Sage J; Khavari PA. 2013. IQGAP1 scaffold-kinase interaction blockade selectively targets RAS-MAP kinase-driven tumors. Nat Med 19(5):626-30. [PubMed: 23603816]  [MGI Ref ID J:198505]

Littlewood TD; Hancock DC; Danielian PS; Parker MG; Evan GI. 1995. A modified oestrogen receptor ligand-binding domain as an improved switch for the regulation of heterologous proteins. Nucleic Acids Res 23(10):1686-90. [PubMed: 7784172]  [MGI Ref ID J:118587]

Pelengaris S; Littlewood T; Khan M; Elia G; Evan G. 1999. Reversible activation of c-Myc in skin: induction of a complex neoplastic phenotype by a single oncogenic lesion. Mol Cell 3(5):565-77. [PubMed: 10360173]  [MGI Ref ID J:55801]

Scholl FA; Dumesic PA; Barragan DI; Charron J; Khavari PA. 2009. Mek1/2 gene dosage determines tissue response to oncogenic Ras signaling in the skin. Oncogene 28(12):1485-95. [PubMed: 19198628]  [MGI Ref ID J:147586]

Serrano M; Lin AW; McCurrach ME; Beach D; Lowe SW. 1997. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88(5):593-602. [PubMed: 9054499]  [MGI Ref ID J:118586]

Tarutani M; Cai T; Dajee M; Khavari PA. 2003. Inducible activation of ras and raf in adult epidermis. Cancer Res 63(2):319-23. [PubMed: 12543782]  [MGI Ref ID J:81660]

Zoumpoulidou G; Broceno C; Li H; Bird D; Thomas G; Mittnacht S. 2012. Role of the tripartite motif protein 27 in cancer development. J Natl Cancer Inst 104(12):941-52. [PubMed: 22556269]  [MGI Ref ID J:189317]

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 maintaining a live colony, hemizygotes are bred to wildtype siblings or to inbred 129S1/SvImJ (Stock No. 002448) mice.

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
   Noncarrier
   002448 129S1/SvImJ (approximate)
 
  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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