caMEK1 Mouse

Tool Details

*FOR RESEARCH USE ONLY

• Tool name: caMEK1 Mouse
• Tool sub type: Mouse
• Disease: Epilepsy
• Conditional: Yes
• Conditional description: For CamK11 cross only Cre expressed under CamKII promoter enables conditional tissue-specific caMEK1 overexpression in the cortex, striatum and hippocampus.
• Description: Disease model for spontaneous epilepsy; in vivo studies of constitutively active form of MEK1, which is conditionally expressed in the murine brain and results in ERK activation. The caMEK1-CamKIICre transgenic mouse exhibits an epileptic phenotype, characterised by frequent, spontaneous seizures from 6-8 weeks of age. Seizures occur throughout the lifetime of the mouse, becoming less frequent in older animals. On average, caMEK1-CamKIICre mice have6.2 seizures per day. The caMEK1-CamKIICre mouse expresses a constitutively activated MAP/ERK Kinase (caMEK1) specifically in neuronal cells of the cortex, striatum and hippocampus of the mouse brain. The epileptic phenotype results from caMEK1-mediated activation of ERK, which positively regulates protein translation (via phosphorylation of eIF4E) and augments translation and protein levels, specifically levels of the N-methyl-D-aspartate receptor (NMDAR) subunit NR2B, a factor which is strongly implicated in epileptogenesis and a promising candidate for anti-epileptic therapies.The caMEK1-CamKIICre mouse gives researchers the opportunity to study both the molecular pathways contributing to epileptogenesis and possible anti-epileptic therapies acting on the ERK pathway/NMDARs.
• Genetic background: A caMEK1 transgene vector, containing a caMEK1 expression cassette preceeded by a loxP flanked resistance cassette, was transfected into 129 ES cells. Properly targeted ES cells containing the transgene were selected, cloned, and injected into C57BL6 blastocysts. Chimeric offspring were backcrossed to establish heterozygous lines. Transgenic mice were mated to CamKII-Cre mice, excising the loxP flanked resistance cassette from the caMEK1 transgene in tissues expressing Cre, and establishing caMEK1-CamKII-Cre mice with cortex-, striatum-, and hippocampus-specific caMEK1 overexpression.
• Phenotype: Neurological abnormalities (epileptic);
• Zygosity: Heterozygous
• Production details: A caMEK1 transgene vector, containing a caMEK1 expression cassette preceeded by a loxP flanked resistance cassette, was transfected into 129 ES cells. Properly targeted ES cells containing the transgene were selected, cloned, and injected into C57BL6 blastocysts. Chimeric offspring were backcrossed to establish heterozygous lines. Transgenic mice were mated to CamKII-Cre mice, excising the loxP flanked resistance cassette from the caMEK1 transgene in tissues expressing Cre, and establishing caMEK1-CamKII-Cre mice with cortex-, striatum-, and hippocampus-specific caMEK1 overexpression.

Handling

• Shipping conditions: Embryo/Spermatoza- Dry Ice

Target Details

• Target: Constitutively active MAP/ERK kinase 1 (caMEK1) mutant

References

• Nateri et al. 2007. EMBO J. 26(23):4891-901. PMID: 17972914.
• ERK activation causes epilepsy by stimulating NMDA receptor activity.