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Strain Name:

129S.B6-Tg(KRT14-RAF1/ESR1)1Pkha/J

Stock Number:

006661

Availability:

Repository- Live

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Former Name      129.B6-Tg(KRT14-RAF1/Esr1)1Pkha/J    (Changed: 13-APR-07 )
Genes & Alleles   ESR1;   KRT14;   RAF1;   Tg(KRT14-RAF1/ESR1)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
Mating System+/+ sibling x Hemizygote         (Female x Male)
Specieslaboratory mouse
Donating Investigator Paul Khavari,   Stanford University
GenerationN6+N1F1 (03-DEC-07)

Strain Description
Mice hemizygous for this "K14-Raf:ER" transgene are viable and fertile. Inducible expression of the human Raf1(Raf-1 [DD]):estrogen receptor (ER) fusion protein is observed in the epidermis following topical application of 4-hydroxytamoxifen (4OHT). Prolonged (4 weeks) induction of human Raf-1[DD] 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. Raf-1[DD]-induced skin abnormalities are entirely reversed within one month after 4OHT cessation. These mice have a similar 4OHT-inducible skin phenotype as the transgenic mice expressing human H-RasG12V (Stock No. 006403) 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 in elucidating cellular events preceding skin cancer cell transformation.

Strain Development
The “K14-Raf:ER” transgene was designed with a 2075-bp human keratin 14 promoter sequence upstream of the constitutively active Y340D/Y341D mutant form of the catalytic domain of human Raf-1 (Raf-1[DD]) fused at its carboxy terminal with the hormone binding domain of the human estrogen receptor. 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-RAF1/ESR1)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
  • thick skin (MGI Ref ID J:81660)
    • with continuous 4-hydroxy-testosterone (4OHT) application, skin thickening is observed after 3 weeks

Gene & Allele Details

Allele Symbol Tg(KRT14-RAF1/ESR1)1Pkha
Allele Name transgene insertion 1, Paul A Khavari
Common Name(s) K14-Raf:ER;
Mutation Made By Paul Khavari,   Stanford University
Strain of OriginC57BL/6
Expressed Gene RAF1, v-raf-1 murine leukemia viral oncogene homolog 1, human
Expressed Gene ESR1, estrogen receptor 1, human
Promoter KRT14, keratin 14 (epidermolysis bullosa simplex, Dowling-Meara, Koebner), human
General Note Three independent transgenic mouse lines were generated that exhibited similar levels of fusion protein expression.
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 RAF1, in which tyrosine is replaced by aspartic acid at amino acid positions 340 and 341 (Y340D/Y341D), joined at its carboxyl terminal to the ligand-binding domain of human estrogen receptor 1. The fusion protein can be activated in the epidermis by topical application of 4-hydroxytamoxifen. [MGI Ref ID J:118584] [MGI Ref ID J:118585] [MGI Ref ID J:81660]

Control Information

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

Genotyping Protocols

Tg(KRT14-RAF1/ESR1)1Pkha

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, hemizygotes are bred to wildtype siblings or to inbred 129S1/SvImJ (Stock No. 002448) mice.
Diet Information LabDiet® 5K52/5K67

Related Strains

View Strains carrying other alleles of ESR1     (7 strains)

View Strains carrying other alleles of KRT14     (10 strains)

Additional Web Information

Congenic Nomenclature

Animal Health Reports

Room Number           AX11

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

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-RAF1/ESR1)1Pkha/J
Stock Number: 006661

Price Details

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Supply Details

Standard SupplyRepository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.
Supply Notes Usually shipped between four and eight weeks of age.
This strain is included in the Induced Mutant Resource Colony collection.
LicensingSee General Terms and Conditions below for Licensing and Use Restrictions  
Control InformationView Control Information in Strain Details.

General Terms and Conditions

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For additional Licensing and Use Restrictions view the link(s) below:
- 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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