Modeling human epilepsies in mice

Two categories of mouse models of human epilepsy are now contributing to th e experimental analysis of inherited seizure disorders. The first type incl udes homologous genetic models arrived at in the classic way; the genes fro m human inherited epilepsy syndromes are cloned, and mice are recreated wit h functionally identical mutations. The second category involves the revers e strategy: mutating single genes in mice and determining whether the newly created nervous system develops epilepsy. These "gene-forward" models defi ne specific candidate genes that can then be tested for possible involvemen t in human epilepsies. Spontaneous mutation of genes in mice and other spec ies is also a source for candidate genes. As each of these genes and their physiologic functions is defined, the focus can shift to (a) fully characte rizing the clinical epilepsy phenotype, (b) tracing the steps in the molecu lar pathogenesis of the disorder, and (c) pinpointing molecular targets for early intervention. Along with providing a unique opportunity to understan d the mechanisms of inherited epileptogenesis, the mouse models serve as id eal biological test systems to search for novel therapeutic strategies.