Developmental impact of a familial GABAA receptor epilepsy mutation

Abstract

Objective: A major goal of epilepsy research is to understand the molecular and functional basis of seizure genesis. A human GABAA γ2 gene mutation (R43Q) is associated with generalized epilepsy. Introduction of this mutation into a mouse by gene targeting recapitulates the human phenotype demonstrating a strong genotype to phenotype link. GABAA receptors play a role in the moment-to-moment control of brain function and also on the long-term wiring of the brain by directing neuronal development. Our objective was to determine whether developmental expression of the mutation alters seizure susceptibility later in life. Methods: A tetracycline-based conditional model for activation of a hypomo..