Autosomal dominant nocturnal frontal-lobe epilepsy

California Institute Of Technology, Pasadena CA

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Abstract

DESCRIPTION (provided by applicant): This project tests the hypothesis that knock-in mice carrying nicotinic receptor mutations linked to autosomal dominant nocturnal frontal-lobe epilepsy (nADNFLE) will display seizures resembling the human disease. Breeding will continue of a knock-in mouse strain harboring a nicotinic receptor alpha4 subunit with the M2 domain Serl0'Leu mutation, which corresponds to one of the five known nADNFLE alleles. This strain will be tested for spontaneous and nicotine-induced seizures using chronic video-EEG monitoring. Pharmacological tests will be performed to assess nicotinic specificity. Additional knock-in mouse strains will be developed that harbor nicotinic receptor beta2 subunits with the M2 domain Va122'Leu and Va122 Met mutations (other nADNFLE alleles) and will also be tested for seizures. If the hypothesis is confirmed, this project will provide an animal model appropriate for detailed pathophysiological studies as well as for testing of new therapeutic drugs, targeted at ADNFLE and at other types of frontal lobe epilepsy.