Cloning of a putative GABAA receptor from cyclodiene-resistant Drosophila: a case study in the use of insecticide-resistant mutants to isolate neuroreceptors.

This chapter uses the isolation and cloning of cyclodiene resistance from Drosophila melanogaster to illustrate how mutants resistant to a toxicant can be used to study neuroreceptors. Isolation of mutants from the field, mapping of the single gene responsible and its subsequent cloning are described. As confirmation of gene cloning a susceptible allele of the gene has been used to genetically transform resistant individuals to susceptibility. The gene product appears to code for a subunit of a receptor highly similar to vertebrate GABAA receptor/chloride ion channels, and functional expression studies are described which will elucidate its pharmacology. Cyclodiene resistance is extremely widespread, occurring in both invertebrates and vertebrates. Thus examination of resistance-associated mutations in this receptor in a range of species will enhance our understanding of both the binding sites of toxic ligands and the genetic basis of pesticide resistance.