Transgenic animal models can reconstruct cellular, biochemical, and molecular alterations associated with human diseases and may help identify key disease mechanisms. Gene disruption, which results in the loss of the functional gene product, is the most common genetic alteration generated by transgenic approaches. Gene disruption can be introduced by random transgene integration or by gene targeting. Both of these approaches have resulted in mice that display recurrent seizures reminiscent of epilepsy. Here, we briefly describe the techniques of random transgene insertion and gene targeting and discuss how these methods were used to generate the epileptic jerky and 5-hydroxytryptamine (5-HT2C) receptor deficient mice. We also analyze how these mutants can contribute to our understanding of the molecular and cellular mechanisms underlying epileptic seizures.
