ffrench-Constant R H
University of Wisconsin-Madison 53706.
EXS. 1993;63:210-23. doi: 10.1007/978-3-0348-7265-2_9.
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.
本章利用从黑腹果蝇中分离和克隆环二烯抗性基因的实例，来说明如何利用对毒物具有抗性的突变体来研究神经受体。文中描述了从野外分离突变体、定位负责该抗性的单个基因并随后进行克隆的过程。作为基因克隆的验证，该基因的一个敏感等位基因已被用于将抗性个体遗传转化为敏感个体。该基因产物似乎编码一种与脊椎动物γ-氨基丁酸A受体/氯离子通道高度相似的受体亚基，并描述了功能表达研究，这些研究将阐明其药理学特性。环二烯抗性极为普遍，在无脊椎动物和脊椎动物中均有发生。因此，研究一系列物种中该受体的抗性相关突变，将增进我们对有毒配体结合位点以及抗药性遗传基础的理解。
