Ataxic mouse mutants and molecular mechanisms of absence epilepsy

Mouse genetic models for common human diseases have been studied for most o f the 20th century. Although many polygenic strain differences and spontane ous single gene mutants have been extensively characterized over the years, knowing their innermost secrets ultimately requires the identity of the mu tated genes. One group of neurological mutants, detected initially clue to cerebellar dysfunction, was identified as models for epilepsy when they wer e unexpectedly found to have spike-wave seizures associated with behavioral arrest, a central feature of absence or petit-mal epilepsy. A further surp rise was that recently identified defective genes encode different subunits of voltage-gated Ca2+ channels (VGCCs), implying common seizure mechanisms . In this review we first consider these spontaneous mutants with VGCC defe cts in the context of other mouse models for epilepsy. Then, from the new w ave of genetic and functional studies of these mutants we discuss their pro spects for yielding insight into the molecular mechanisms of epilepsy.