| Human seizure disorders pose a significant health problem because of the large numbers of afflicted individuals and the complexity of the various subtypes of the disease. While great leaps have been made in recent years in deciphering the underlying causes of the disease and in its treatment, much still remains to be learned about the genetic and physiological basis of the disorder, and the search is also continuing for better and more effective anticonvulsants. One particular class of Drosophila behavioral mutants, the bang-sensitives (BS), could potentially aid in this endeavor since they are much more susceptible to convulsions than wild-type flies and their seizures appear to have significant similarities with that observed in mammals. With the powerful genetic and molecular methodologies available to Drosophila, these mutants may be extremely useful to dissect the etiology of the disorder and thereby pave the way to more effective treatments.; In this study, I present the results of an investigation centering on a particular BS mutant, slamdance (sda). I first report the cloning and characterization of the gene, which was found to be the Drosophila homolog of human aminopeptidase N. The study then switches to an analysis of the interaction between sda and laminin, a prominent extracellular molecule found to bind to the aminopeptidase both in vitro and in vivo. Of particular interest in this sub-study is a postulation of a mechanistic hypothesis for the genesis of seizures seen in sda, with the aminopeptidase possibly functioning as a guidance molecule during neuronal development. Finally, I demonstrate the utility of using the BS mutants as a tool to screen novel anticonvulsants by showing that the seizures of a particular mutant, bang senseless (bss), can be significantly ameliorated with the administration of a known anticonvulsant, potassium bromide. Together, these findings have broadened our knowledge of the BS mutants, brought forth an intriguing mechanistic role of a previously unsuspected molecule, and perhaps laid the foundation for using these mutants in a clinical capacity to help search for new anticonvulsants. |
