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Strain Name:

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

Stock Number:

006403

Availability:

Repository-Cryopreserved

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Genes & Alleles   Esr1;   HRAS;   KRT14;   Tg(KRT14-Esr1/HRAS)1Pkha;

Product Information

Strain Details

Type JAX® GEMM® Strain - Congenic
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Mutant Strain
Type JAX® GEMM® Strain - Transgenic
Specieslaboratory mouse
Donating Investigator Paul Khavari,   Stanford University
GenerationN6pN1

Strain Description
Mice hemizygous for this "K14-ER:Ras" transgene are viable and fertile. Inducible expression of the ER:Ras fusion protein is observed in the epidermis following topical application of 4-hydroxytamoxifen (4OHT). 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.

Strain 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.

Mammalian Phenotype Terms assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

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

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

Gene & Allele Details

Allele Symbol Tg(KRT14-Esr1/HRAS)1Pkha
Allele Name transgene insertion 1, Paul A Khavari
Common Name(s) K14-ER:Ras;
Mutation Made By Paul Khavari,   Stanford University
Strain of OriginC57BL/6
Expressed Gene Esr1, estrogen receptor 1 (alpha), mouse, laboratory
Expressed Gene HRAS, v-Ha-ras Harvey rat sarcoma viral oncogene homolog, human
Promoter KRT14, keratin 14 (epidermolysis bullosa simplex, Dowling-Meara, Koebner), 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]

Control Information

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

Genotyping Protocols

Tg(KRT14-Esr1/HRAS)1Pkha

Colony Maintenance

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

Related Strains

View Strains carrying other alleles of Esr1     (10 strains)

Strains carrying other alleles of HRAS
002409   B6;SJL-Tg(Wap-HRAS)69Lln Chr YSJL/J
002410   FVB.Cg-Tg(Wap-HRAS)69Lln Chr YSJL/J
View Strains carrying other alleles of HRAS     (2 strains)

View Strains carrying other alleles of KRT14     (10 strains)

Additional Web Information

Congenic Nomenclature

Research Applications

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

Cancer Research
Genes Regulating Growth and Proliferation
Other

Cell Biology Research
Genes Regulating Growth and Proliferation
Signal Transduction

Dermatology Research
Other

Research Tools
Cancer Research
Cell Biology Research
Dermatology Research

HRAS related

Cancer Research
Increased Tumor Incidence (Mammary Gland Tumors: males only)
Oncogenes

References

Selected Reference(s)

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]

Additional References

Price and Supply Information

Strain Name: 129S.B6-Tg(KRT14-Esr1/HRAS)1Pkha/J
Stock Number: 006403

Price Details

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Supply Details

Standard SupplyRepository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.
Supply Notes Cryorecovery - Standard.
The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services: Tel: 1-800-422-6423 or 1-207-288-5845; Email: jaxservices@jax.org.
This strain is included in the Induced Mutant Resource Colony collection.
Genomic DNA is available for this strain from the Mouse DNA Resource.

LicensingSee General Terms and Conditions below for Licensing and Use Restrictions  
Control InformationView Control Information in Strain Details.

General Terms and Conditions

View JAX® Mice & Services Conditions of Use.

For additional Licensing and Use Restrictions view the link(s) below:
- Notice Regarding cre/Esr1 (Tamoxifen Inducible Cre) Strains.
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

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.
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