Seizure disorders in mutant mice: relevance to human epilepsies

The rate at which mutant genes producing an epileptic phenotype in mice hav e been identified over the past few years has been astounding. Manipulating the genome of mice has led to identification of a diversity of genes whose absence or modification either causes epileptic seizures or, conversely, l imits epileptogenesis. In addition, positional cloning of genes in which sp ontaneously arising mutations cause epilepsy in mice has led to the identif ication of genes encoding voltage- and ligand-gated ion channels. Finally, engineering a mutation that mimics a rare form of human epilepsy has led to a mouse line with a phenotype similar to that of the human disease. Taken together, these discoveries promise to shed light on the mechanisms underly ing genetic control of neuronal excitability, suggest candidate genes under lying genetic forms of human epilepsy, and provide a valuable model with wh ich to elucidate how the genotype produces the phenotype of a rare form of human epilepsy.