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Strain Name:

FVB-Tg(KRT14-MAP2K1/Esr1)12Pkha/J

Stock Number:

006822

Availability:

Repository- Live

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Genes & Alleles   Esr1;   KRT14;   MAP2K1;   Tg(KRT14-MAP2K1/Esr1)12Pkha;

Product Information

Strain Details

Type JAX® GEMM® Strain - Coisogenic
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Mutant Strain
Type JAX® GEMM® Strain - Transgenic
Mating SystemNoncarrier x Hemizygote         (Female x Male)
Specieslaboratory mouse
Donating Investigator Paul Khavari,   Stanford University
GenerationN9+ (15-MAY-07)

Strain Description
Mice hemizygous for this "K14-Mek1:ER" transgene are viable and fertile. Following topical application of 4-hydroxytamoxifen (4OHT), increased epidermal expression of the Mek1:ER fusion protein is observed. Induction of this constitutively active form of human Map2k1 (Mek1R4F) promotes the undifferentiated, proliferative phenotypic characteristics (including hyperplasia, increased levels of phosphorylated ERK1/2, increased mitotic index, decreased expression of differentiation markers and increased expression of beta-1 and beta-4 integrin subunits) observed in epidermal neoplasia in as few as 5 days. Mek1R4F-induced skin abnormalities were entirely reversed within ten days after 4OHT administration cessation. These mice have a similar 4OHT-inducible skin phenotype as the transgenic mice expressing human H-RasG12V (Stock No. 006403) or human Raf-1[DD] (Stock No. 006661), 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-Mek1:ER” transgene was designed with a 2075-bp human keratin 14 promoter sequence upstream of the constitutively active mutant region from human mitogen activated protein kinase-kinase 1 (Mek1R4F; containing an amino-terminal deletion of aa 32-51 and the S218E/S222D substitutions) fused at its carboxy 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 FVB embryos and chimeric founders were established. Mice from founder line 12 were then backcrossed to FVB inbred mice for at least 8 generations prior to arrival at The Jackson Laboratory.

Mammalian Phenotype Terms assigned by genotype

Tg(KRT14-MAP2K1/Esr1)12Pkha/0

        involves: FVB
  • skin/coat/nails phenotype
  • epidermal hyperplasia (MGI Ref ID J:92407)
    • topical application of 4-hydroxy-testosterone (4OHT) results in development of epidermal hyperplasia after 5 days; this remains stable after a further month of treatment, and is reversed upon cessation of 4OHT treatment

Gene & Allele Details

Allele Symbol Tg(KRT14-MAP2K1/Esr1)12Pkha
Allele Name transgene insertion 12, Paul A Khavari
Common Name(s) CA-Mek1:ER; CA-Mek1:ER (line 12); K14-Mek1:ER (line 12); M1E-12; Mek1:ER;
Mutation Made By Paul Khavari,   Stanford University
Strain of OriginFVB
Expressed Gene Esr1, estrogen receptor 1 (alpha), mouse, laboratory
Expressed Gene MAP2K1, mitogen-activated protein kinase kinase 1, human
Promoter KRT14, keratin 14 (epidermolysis bullosa simplex, Dowling-Meara, Koebner), human
General Note Of three PCR-confirmed transgenic mouse lines, two - designated lines 12 and 13 - express the fusion protein in skin. Topical tamoxifen treatment induces similar skin phenotypes in both lines that are more severe in line 12, which was therefore used in further studies.
Molecular Note The transgene contains a 2075-bp human keratin 14 promoter construct with a 5' intron from a beta-globin gene driving expression of a cDNA that encodes a constitutively active mutant human mitogen activated protein kinase-kinase 1 (with deletion of aminoacids 32-51, which comprise a putative alpha-helical domain, and the amino acid substitutions Ser218Glu and Ser222Asp, which remove phosphorylatively regulable serines). This is joined at its COOH-terminal with the Gly525Arg mutant ligand binding domain of the mouse estrogen receptor (ERTM), which renders the fusion protein's activity inducible by 4-hydroxytamoxifen, but unresponsive to natural estrogen (17beta-estradiol). [MGI Ref ID J:118584] [MGI Ref ID J:118587] [MGI Ref ID J:118713] [MGI Ref ID J:118714] [MGI Ref ID J:92407]

Control Information

  Control
   Noncarrier
   001800 FVB/NJ
 
  Considerations for Choosing Controls

Genotyping Protocols

Tg(KRT14-MAP2K1/Esr1)12Pkha

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, hemizygotes are bred to wildtype siblings or to inbred FVB/NJ (Stock No. 001800) mice.
Diet Information LabDiet® 5K52/5K67

Related Strains

View Strains carrying other alleles of Esr1     (10 strains)

View Strains carrying other alleles of KRT14     (10 strains)

Strains carrying other alleles of MAP2K1
006662   C57BL/6-Tg(ACTB-MAP2K1*K97M)1Stl/J
View Strains carrying other alleles of MAP2K1     (1 strain)

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)

Scholl FA; Dumesic PA; Khavari PA. 2004. Mek1 alters epidermal growth and differentiation. Cancer Res 64(17):6035-40. [PubMed: 15342384]  [MGI Ref ID J:92407]

Additional References

Price and Supply Information

Strain Name: FVB-Tg(KRT14-MAP2K1/Esr1)12Pkha/J
Stock Number: 006822

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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- Use of MICE by companies or for-profit entities requires a license prior to shipping.

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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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