title: Cyp12a4 confers lufenuron resistance in a natural population of Drosophila melanogaster.
abstract: Lufenuron is an insect growth regulator insecticide mainly used for the control of the cat flea. To understand mechanisms of resistance to lufenuron, we have characterized lufenuron resistance in a natural population of Drosophila melanogaster. In this study we have used precise genetic mapping to identify a mechanism of lufenuron resistance: the overexpression of the cytochrome P450 gene Cyp12a4. Cyp12a4 is predicted to encode a mitochondrial cytochrome P450 enzyme. Expression of Cyp12a4 in D. melanogaster third-instar larvae was detected in the midgut and Malpighian tubules of both lufenuron-resistant and wild-type strains. The level of Cyp12a4 expression in the midgut is higher in the lufenuron-resistant strain than in wild-type strains. Driving the expression of Cyp12a4 in the midgut and Malpighian tubules by using the GAL4/UAS gene expression system results in lufenuron resistance, but it does not result in resistance to three other insecticide classes. Transgenic expression of Cyp12a4 in a ubiquitous expression pattern results in late embryonic lethality, suggesting that high-level ectopic expression of Cyp12a4 is detrimental to development.
authors.affiliation: Centre for Environmental Stress and Adaptation Research, Department of Genetics, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, 30 Flemington Road, Parkville, Victoria 3010, Australia.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bogwitz
authors.forename: Henry
authors.initials: H
authors.lastname: Chung
authors.forename: Lorin
authors.initials: L
authors.lastname: Magoc
authors.forename: Sheena
authors.initials: S
authors.lastname: Rigby
authors.forename: Wayn
authors.initials: W
authors.lastname: Wong
authors.forename: Melanie
authors.initials: M
authors.lastname: O'Keefe
authors.forename: John A
authors.initials: JA
authors.lastname: McKenzie
authors.forename: Philip
authors.initials: P
authors.lastname: Batterham
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Daborn
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001549:Benzamides / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D004351:Drug Resistance; D015870:Gene Expression; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D017403:In Situ Hybridization; D007814:Larva / Q000201:enzymology; D008928:Mitochondria / Q000201:enzymology; D008969:Molecular Sequence Data; D020161:Physical Chromosome Mapping; D017422:Sequence Analysis, DNA; D015996:Survival Rate; D005466:Fluorocarbons
chemical_list: D001549:Benzamides; D003577:Cytochrome P-450 Enzyme System; D029721:Drosophila Proteins; C070364:fluphenacur; D005466:Fluorocarbons; C504979:cytochrome P-450 12A4, Drosophila