Genes Underlying Monogenic and Multigenic Epilepsies in Mice

Epilepsies are defined as a group of disorders with recurrent seizures. It is now well-established from human studies that a good proportion of these epilepsies are inherited. The same finding is true for mice as there are several examples of mouse models showing monogenic and multigenic inheritance of epilepsy. This article reviews the recent developments in mouse positional cloning leading to the identification of many epilepsy-related genes in monogenic absence and convulsive seizure models of the mouse. Surprisingly, four of the six known absence seizure mouse models have mutations in the voltage-dependent calcium channel subunit genes. In contrast, mice with spontaneous single gene and targeted gene disruptions causing convulsive seizures reveal an assortment of genes, including those encoding ion channels, transcription factors, myelin and vesicle proteins. For the more complex seizure models with multiple gene defects, quantitative trait loci have been identified but the underlying genes have yet to be found. The challenges of fine-mapping and locating the genes for these traits are also discussed.