Ashok M, Turner C, Wilson T G
Department of Biology, Colorado State University, Fort Collins, CO 80523, USA.
Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):2761-6. doi: 10.1073/pnas.95.6.2761.
Juvenile hormone analog (JHA) insecticides are relatively nontoxic to vertebrates and offer effective control of certain insect pests. Recent reports of resistance in whiteflies and mosquitoes demonstrate the need to identify and understand genes for resistance to this class of insect growth regulators. Mutants of the Methoprene-tolerant (Met) gene in Drosophila melanogaster show resistance to both JHAs and JH, and previous biochemical studies have demonstrated a mechanism of resistance involving an intracellular JH binding-protein that has reduced ligand affinity in Met flies. We cloned the Met+ gene by transposable P-element tagging and found reduced transcript level in several mutant alleles, showing that underproduction of the normal gene product can lead to insecticide resistance. Transformation of Met flies with a Met+ cDNA resulted in susceptibility to methoprene, indicating that the cDNA encodes a functional Met+ protein. MET shows homology to the basic helix-loop-helix (bHLH)-PAS family of transcriptional regulators, implicating MET in the action of JH at the gene level in insects. This family also includes the vertebrate dioxin receptor, a transcriptional regulator known to bind a variety of environmental toxicants. Because JHAs include a diverse array of chemicals with JH activity, a mechanism whereby they can exert effects in insects through a common pathway is suggested.
保幼激素类似物（JHA）杀虫剂对脊椎动物相对无毒，并能有效防治某些害虫。近期有关粉虱和蚊子产生抗性的报道表明，有必要鉴定和了解对这类昆虫生长调节剂产生抗性的基因。黑腹果蝇中耐甲氧普烯（Met）基因的突变体对JHA和保幼激素（JH）均表现出抗性，先前的生化研究已经证明了一种抗性机制，该机制涉及一种细胞内JH结合蛋白，其在Met果蝇中的配体亲和力降低。我们通过转座P因子标签克隆了Met⁺基因，并在几个突变等位基因中发现转录水平降低，这表明正常基因产物产量不足会导致对杀虫剂产生抗性。用Met⁺ cDNA转化Met果蝇会使其对甲氧普烯敏感，这表明该cDNA编码一种功能性Met⁺蛋白。MET与转录调节因子的碱性螺旋-环-螺旋（bHLH）-PAS家族具有同源性，这表明MET在昆虫基因水平上参与JH的作用。该家族还包括脊椎动物二噁英受体，一种已知能结合多种环境毒物的转录调节因子。由于JHA包括一系列具有JH活性的化学物质，因此提出了一种它们可以通过共同途径在昆虫中发挥作用的机制。
