The DrosophilaslamdanceGene: A Mutation in an Aminopeptidase Can Cause Seizure, Paralysis and Neuronal Failure

We report here the characterization of slamdance (sda), a Drosophila melanogaster “bang-sensitive” (BS) paralytic mutant. This mutant exhibits hyperactive behavior and paralysis following a mechanical “bang” or electrical shock. Electrophysiological analyses have shown that this mutant is much more prone to seizure episodes than normal flies because it has a drastically lowered seizure threshold. Through genetic mapping, molecular cloning, and RNA interference, we have demonstrated that the sda phenotype can be attributed to a mutation in the Drosophila homolog of the human aminopeptidase N (APN) gene. Furthermore, using mRNA in situ hybridization and LacZ staining, we have found that the sda gene is expressed specifically in the central nervous system at particular developmental stages. Together, these results suggest that the bang sensitivity in sda mutants is caused by a defective APN gene that somehow increases seizure susceptibility. Finally, by using the sda mutation as a sensitized background, we have been able to identify a rich variety of sda enhancers and other independent BS mutations.