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7051035 
Journal Article 
Cyp12a4 confers lufenuron resistance in a natural population of Drosophila melanogaster 
Hooper, HL; Sibly, RM; Hutchinson, L; Maund, SJ; Wong, W; O'Keefe, M; Mckenzie, JA; Batterham, P; Daborn, PJ; , 
2005 
Proceedings of the National Academy of Sciences of the United States of America 
NATL ACAD SCIENCES 
WASHINGTON 
102 
36 
12807-12812 
English 
16120680 
WOS:000231716700031 
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.