Cyp12a4 confers lufenuron resistance in a natural population of Drosophila melanogaster.
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.
Bogwitz
Michael R
MR
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.
Chung
Henry
H
Magoc
Lorin
L
Rigby
Sheena
S
Wong
Wayn
W
O'Keefe
Melanie
M
McKenzie
John A
JA
Batterham
Philip
P
Daborn
Phillip J
PJ
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
D001549:Benzamides; D003577:Cytochrome P-450 Enzyme System; D029721:Drosophila Proteins; C070364:fluphenacur; D005466:Fluorocarbons; C504979:cytochrome P-450 12A4, Drosophila