INCREASED TRANSCRIPTION OF CYP6D1 CAUSES CYTOCHROME-P450 MEDIATED INSECTICIDE RESISTANCE IN-HOUSE FLY

Insecticide resistance is a major problem that continues to plague eff orts to control pests of animals and crops. An important mechanism by which insects become resistant to insecticides is via increased detoxi fication mediated by the cytochrome P450 microsomal monooxygenases (mo nooxygenases). One of the fundamental gaps in our knowledge about this resistance mechanism is an understanding of how insects express high levels of the specific cytochrome P450(s) responsible for. resistance. One. such P450, CYP6D1, causes resistance to pyrethroid insecticides in the house fly and is expressed at 9-fold higher levels (mRNA and pr otein) in the Learn Pyrethroid Resistant (LPR) strain (compared to sus ceptible strains). The relative stability of CYP6D1 mRNA in resistant and susceptible strains was measured following inhibition of transcrip tion with actinomycin D. The same time course of decrease in CYP6D1 mR NA abundance was detected in both strains indicating that the high lev el of expression of CYP6D1 in LPR is not due to increased stability of the mRNA. The comparative rates of transcription of CYP6D1 were measu red using an in vitro run-on transcription assay. The relative amount of CYP6D1 transcript produced in this assay was 10-fold greater in the LPR strain compared to the susceptible strain. This demonstrates that increased transcription of CYP6D1 is an underlying cause of monooxyge nase-mediated insecticide resistance. The increased rate of transcript ion of CYP6D1 in the resistant strain (LPR) is controlled by two facto rs: one on autosome 1 and another on autosome 2. (C) 1998 Elsevier Sci ence Ltd. All rights reserved.