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- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- 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. Species laboratory mouse Generation N6+N1F1pN1
Generation DefinitionsDonating 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
Strains carrying other alleles of ESR1
View Strains carrying other alleles of ESR1 (30 strains)
006403 129S.B6-Tg(KRT14-Esr1/HRAS)1Pkha/J 004853 B6.C3-Tg(KRT14-Birc5)19Gros/J 009687 B6.Cg-Tg(KRT14-Kitl*)4XTG2Bjl/J 007622 B6;SJL-Tg(KRT14-Hr)551Cct/J 007678 B6;SJL-Tg(KRT14-rtTA)208Jek/J 002980 C57BL/6-Tg(Cd152Ig)1Jbs/J 006822 FVB-Tg(KRT14-MAP2K1/Esr1)12Pkha/J 005705 FVB-Tg(KRT14-Vegfa)3Dtm/J 008099 FVB-Tg(KRT14-rtTA)F42Efu/J 017005 FVB.Cg-Tg(KRT14-Fyn*)aJsey/J 004782 STOCK Tg(KRT14-cre)1Amc/J 005107 STOCK Tg(KRT14-cre/ERT)20Efu/J
018449 B6;CBA-Tg(Mpz-RAF1/ESR1)A668Ayld/J
Additional Web Information
Use of MICE by companies or for-profit entities requires a license prior to shipping.
Phenotype
Phenotype Information
- 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. Estrogen Receptor 1; ESR1 (ESR1)
Leopard Syndrome 2 (RAF1)
Migraine with or without Aura, Susceptibility to, 1 (ESR1)
Myocardial Infarction, Susceptibility to (ESR1)
Noonan Syndrome 5; NS5 (RAF1)
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/6This 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 (random, expressed) | ||
| Common Name(s) | K14-Raf:ER; | ||
| Mutation Made By | Paul Khavari, Stanford University | ||
| Strain of Origin | C57BL/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, 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 relatedBosch 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 & Husbandry When 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 |
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Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2250.00 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 11 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 |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2925.00 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 11 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).
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Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
General Supply Notes
- Genomic DNA is available for this strain from the Mouse DNA Resource.
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'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
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Contact information
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| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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
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