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.
University of Wisconsin-Madison 53706.
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D000818:Animals; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D004330:Drosophila / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D004351:Drug Resistance / Q000235:genetics*; D016678:Genome; D006843:Hydrocarbons, Chlorinated; D007306:Insecticides / Q000494:pharmacology*; D016296:Mutagenesis; D009420:Nervous System / Q000187:drug effects; D009424:Nervous System Physiological Phenomena; D011963:Receptors, GABA-A / Q000235:genetics* / Q000502:physiology; D013045:Species Specificity
D006843:Hydrocarbons, Chlorinated; D007306:Insecticides; D011963:Receptors, GABA-A; D004247:DNA