Strain Name:

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

Stock Number:

006661

Order this mouse

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

Former Names 129.B6-Tg(KRT14-RAF1/Esr1)1Pkha/J    (Changed: 13-APR-07 )
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
GenerationN6+N1F1pN1
Generation Definitions
 
Donating Investigator Paul Khavari,   Stanford University

Description
Mice hemizygous for this "K14-Raf:ER" transgene are viable and fertile, with expression of the Raf:ER fusion protein (a constitutively active Y340D/Y341D mutant form of the catalytic domain of human Raf-1 (Raf-1[DD]) fused at its carboxy terminal with the G525R mutant human estrogen receptor ligand binding domain (ERTM)) directed to epidermis by the human keratin 14 promoter. Because of the ERTM region of the fusion protein, Raf:ER is restricted to the cytoplasm and the biochemical activity of the Raf:ER fusion gene can be induced following tamoxifen administration. For example, 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.

The G525R mutant 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-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.

Control Information

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

Related Strains

View Strains carrying other alleles of ESR1     (31 strains)

View Strains carrying other alleles of KRT14     (13 strains)

Strains carrying other alleles of RAF1
018449   B6;CBA-Tg(Mpz-RAF1/ESR1)A668Ayld/J
View Strains carrying other alleles of RAF1     (1 strain)

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.
Breast Cancer   (ESR1)
Estrogen Receptor 1; ESR1   (ESR1)
Estrogen Resistance; ESTRR   (ESR1)
Leopard Syndrome 2   (RAF1)
Migraine with or without Aura, Susceptibility to, 1   (ESR1)
Myocardial Infarction, Susceptibility to   (ESR1)
Noonan Syndrome 5; NS5   (RAF1)
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-RAF1/ESR1)1Pkha/0

        involves: C57BL/6
  • integument phenotype
  • hyperkeratosis
    • with continuous 4-hydroxy-testosterone (4OHT) application, hyperkeratosis is observed after 3 weeks   (MGI Ref ID J:81660)
  • thick skin
    • with continuous 4-hydroxy-testosterone (4OHT) application, skin thickening is observed after 3 weeks   (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-RAF1/ESR1)1Pkha
Allele Name transgene insertion 1, Paul A Khavari
Allele Type Transgenic (Constitutively active, Inducible, Inserted expressed sequence)
Common Name(s) K14-Raf:ER;
Mutation Made By Paul Khavari,   Stanford University
Strain of OriginC57BL/6
Expressed Gene RAF1, Raf-1 proto-oncogene, serine/threonine kinase, human
Expressed Gene ESR1, estrogen receptor 1, human
Promoter KRT14, keratin 14, 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]
 
 
 

Genotyping

Genotyping Information

Genotyping Protocols

Tg(KRT14-RAF1/Esr1)1Pkja/J, Melt Curve Analysis
Tg(KRT14-RAF1/ESR1)1Pkha, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

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

Tg(KRT14-RAF1/ESR1)1Pkha related

Bosch E; Cherwinski H; Peterson D; McMahon M. 1997. Mutations of critical amino acids affect the biological and biochemical properties of oncogenic A-Raf and Raf-1. Oncogene 15(9):1021-33. [PubMed: 9285556]  [MGI Ref ID J:118585]

Scholl FA; Dumesic PA; Barragan DI; Harada K; Bissonauth V; Charron J; Khavari PA. 2007. Mek1/2 MAPK kinases are essential for Mammalian development, homeostasis, and Raf-induced hyperplasia. Dev Cell 12(4):615-29. [PubMed: 17419998]  [MGI Ref ID J:122484]

Woods D; Parry D; Cherwinski H; Bosch E; Lees E; McMahon M. 1997. Raf-induced proliferation or cell cycle arrest is determined by the level of Raf activity with arrest mediated by p21Cip1. Mol Cell Biol 17(9):5598-611. [PubMed: 9271435]  [MGI Ref ID J:118584]

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 wild-type 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.
 

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.


See Terms of Use tab for General Terms and Conditions


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.
Ordering Information
JAX® Mice
Surgical and Preconditioning Services
JAX® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use


General Terms and Conditions


For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries regarding Terms of Use

Contracts Administration

phone:207-288-6470

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED “AS IS”. JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.


(6.8)