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

Stock number: 006662
Product name: dnMEK1
Research areas: Cell Biology Research, Neurobiology Research, Research Tools

Description

These mutant mice possess a Lox-STOP-Lox cassette controlling the inserted human dominant-negative mutant form of human MEK1. This strain may be useful for generating conditional mutations in studies involving synaptic plasticity and memory.

Detailed 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.

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.

Allele

Symbol: Tg(ACTB-MAP2K1*K97M)1Stl
Name: transgene insertion 1, Susumu Tonegawa
MGI accession ID: MGI:3707556
Generation method: Transgenic
Attributes: Dominant negative; Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(ACTB-MAP2K1*K97M)1Stl
Marker name: transgene insertion 1, Susumu Tonegawa
Chromosome: UN
Strain of origin: C57BL/6
Expressed genes: MAP2K1,mitogen-activated protein kinase kinase 1,human
Site of expression: Cre excision results in the removal of a stop codon, enabling kinase expression.
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).