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Strain Name:

C57BL/6-Tg(ACTB-MAP2K1*K97M)1Stl/J

Stock Number:

006662

Availability:

Repository- Live


General Terms and Conditions

Genes & Alleles   ACTB;   MAP2K1;   Tg(ACTB-MAP2K1*K97M)1Stl;


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 System+/+ sibling x Hemizygote         (Female x Male)
Specieslaboratory mouse
Donating Investigator Susumu Tonegawa,   Massachusetts Institute of Technology
Generation?+F0 (28-DEC-07)

Strain Description
Hemizygous mice are viable and fertile. These "dnMEK1" mice express a dominant-negative mutant (K97M) form of human MEK1 (synonym: MAP2K1) following Cre-mediated removal of the upstream "Lox-STOP-Lox" cassette; when transgenic mice are bred to a cre-expressing strain, the "floxed stop" cassete is excised in the resulting offspring, and mutant MEK1 expression is observed in the cre-expressing tissue(s). In the absence of Cre recombinase, transgene expression is not detectable in the brains of these "floxed" mice Because the MEK1 mutation abolishes the protein's kinase activity but preserves its ability to interact with ERK1 and ERK2, these transgenic mice may be useful in studying MEK-dependent activation and regulation of ERK, the ERK-MAPK signaling pathway, and neurological studies involving synaptic plasticity and memory.

When bred to a strain expressing Cre recombinase in the CA1 pyramidal cell layer of the hippocampus (see Stock No. 005359 for example), this mutant mouse strain exhibits abnormal learning, memory and synaptic transmission.

Strain Development
A dominant-negative human MEK1 (or MAP2K1) cDNA bearing a K97M mutation (at the ATP binding site) and the SV40 late polyadenylation signal was inserted downstream of a chicken beta-actin-loxP-stop-loxP sequence. The transgene was injected into C57BL/6 embryos. The resulting transgenic mice were subsequently bred to C57BL/6 mice and maintained on that genetic background for many generations prior to arrival at The Jackson Laboratory.

Mammalian Phenotype Terms assigned by genotype

The following phenotype relates to a compound genotype created using this strain.
Contact JAX® Services jaxservices@jax.org for customized breeding options.

Tg(ACTB-MAP2K1*K97M)1Stl/0 Tg(Camk2a-cre)T29-1Stl/0

        involves: BALB/c * C57BL/6   (conditional)
  • behavior/neurological phenotype
  • abnormal contextual conditioning (MGI Ref ID J:88546)
    • when tested for retention 24 hours after contextual fear conditioning, mutants show reduced levels of freezing relative to wild type (mutant - 36.6% vs wild type - 57.5%)
  • abnormal cued conditioning behavior (MGI Ref ID J:88546)
    • 48 hours after a cued fear conditioning test, where a tone was the conditioned stimulus, mutants show a low level of freezing prior to tone presentation, indicating impairment of contextual memory
  • abnormal spatial learning (MGI Ref ID J:88546)
    • in the Morris water maze test, mutants showed a tendency toward longer escape latencies compared to wild type
    • in probe trials with the platform hidden, mutant mice spend less time searching the target quadrant, and show less accurate identification of the precise platform location by having a reduced number of platform crossings
  • nervous system phenotype
  • abnormal excitatory postsynaptic potential (MGI Ref ID J:88546)
    • field EPSPs in mutant hippocampal slice preparations return to levels near unstimulated levels by 3 hours posttetaniziation, while in control slices the fEPSPs (ie. late LTP remains elevated
  • abnormal long term potentiation (MGI Ref ID J:88546)
    • application of 4 trains of tetanic stimulation at 5 minute intervals, elicits long-lasting (>3 hours) potentiation in control hippocampal slices, but in mutants potentiation is unstable and decays progressively
    • mutants display selective impairment in translational component of late-LTP (L-LTP); the defect is transcription-independent, translation-dependent, as shown by difference in inhibition kinetics of actinomycin-D (transcriptional inhibitor) and anisomycin (translational inhibitor)
  • homeostasis/metabolism phenotype
  • abnormal enzyme/coenzyme activity (MGI Ref ID J:88546)
    • ERK activation in the forebrain is inhibited, causing selective deficits in hippocampal memory retention and translation-dependent phase of late-LTP

Gene & Allele Details

Allele Symbol Tg(ACTB-MAP2K1*K97M)1Stl
Allele Name transgene insertion 1, Susumu Tonegawa
Common Name(s) dnMEK1;
Strain of OriginC57BL/6
Site of ExpressionCre excision results in the removal of a stop codon, enabling kinase expression.
Expressed Gene MAP2K1, mitogen-activated protein kinase kinase 1, human
Promoter ACTB, actin, beta, chicken
Molecular Note The transgene encodes a dominant-negative mutant (K97M) form of human MEK1 (or MAP2K1). Expression under the control of the chicken Actin beta promoter occurs only following Cre-mediated removal of the upstream Lox-STOP-Lox cassette. In the absence of Cre recombinase, the transgene is not detectably expressed in the brains of these floxed mice. If bred to a Cre-expressing strain, the floxed stop region is excised in the resulting offspring, and mutant MEK1 expression is observed in the cre-expressing tissue(s). [MGI Ref ID J:88546]

Control Information

  Control
   Noncarrier
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Genotyping Protocols

Tg(Sv40 splicing/polyadenylation)

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, hemizygotes are bred to wildtype siblings or to C57BL/6J inbred mice.
Diet Information LabDiet® 5K52/5K67

Related Strains

View Strains carrying other alleles of ACTB     (31 strains)

Strains carrying other alleles of MAP2K1
006822   FVB-Tg(KRT14-MAP2K1/Esr1)12Pkha/J
View Strains carrying other alleles of MAP2K1     (1 strain)

Additional Web Information

Cre-lox or FLP-FRT Systems

Animal Health Reports

Room Number           AX11

Research Applications

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

Cell Biology Research
Signal Transduction
Transcriptional Regulation

Neurobiology Research
Behavioral and Learning Defects
Cre-lox System (loxP-flanked Sequences)
Neurotransmitter Receptor and Synaptic Vesicle Defects

Research Tools
Cell Biology Research
Cre-lox System (loxP-flanked Sequences)
Genetics Research (Mutagenesis and Transgenesis: transcriptional activation)

References

Selected Reference(s)

Kelleher RJ rd; Govindarajan A; Jung HY; Kang H; Tonegawa S. 2004. Translational control by MAPK signaling in long-term synaptic plasticity and memory. Cell 116(3):467-79. [PubMed: 15016380]  [MGI Ref ID J:88546]


Price and Supply Information

Strain Name: C57BL/6-Tg(ACTB-MAP2K1*K97M)1Stl/J
Stock Number: 006662

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

View JAX® Mice & Services Conditions of Use.

Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.

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.

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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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