title: Animal models for autosomal dominant frontal lobe epilepsy: on the origin of seizures.
abstract: Autosomal dominant frontal lobe epilepsy (ADNFLE) can be caused by mutations in either the α4 or β2 subunit of the neuronal nicotinic Ach receptor. In vitro expression studies in Xenopus oocytes or human embryonic kidney cells have been proven to be valuable tools for the characterization of these mutations, but they do not fully resemble the situation in vivo. Compared with them, animal models have the advantage that the functional consequences of a given mutation can be studied in the complex context of an intact living organism. Recent transgenic and knock-in animal models and their valuable contributions to our current understanding of ADNFLE epileptogenesis are discussed in this article. Several of the mouse and rat models support the hypothesis that ADNFLE mutations cause seizures mainly by increasing GABAergic inhibition, and a conditional knock-in mouse model adds early embryonal structural changes as another possible pathogenetic mechanism.
authors.affiliation: Institute of Human Genetics, University Hospital, Ludwig-Maximilians-University of Munich, Goethestrasse 29, Munich, Germany. ortrud.steinlein@med.uni-muenchen.de
authors.forename: Ortrud K
authors.initials: OK
authors.lastname: Steinlein
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D017034:Epilepsy, Frontal Lobe / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D018756:GABA Antagonists / Q000378:metabolism / Q000494:pharmacology; D005799:Genes, Dominant; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D051381:Rats; D011978:Receptors, Nicotinic / Q000235:genetics* / Q000378:metabolism; D012640:Seizures / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D018756:GABA Antagonists; D011978:Receptors, Nicotinic