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Anopheles gambiae P450 reductase is highly expressed in oenocytes and in vivo knockdown increases permethrin susceptibility

Authors

  • G. J. Lycett,

    1. European Molecular Biology Laboratory, Meyerhofstrasse 1, Heidelberg D-69117, Germany;
    2. Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, Vassilika Vouton, 711 10 Heraklion, Crete, Greece;
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    • These authors contributed equally to this work.

  • L. A. McLaughlin,

    1. Biomedical Research Centre, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK
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    • These authors contributed equally to this work.

  • H. Ranson,

    1. Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK
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  • J. Hemingway,

    1. Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK
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  • F. C. Kafatos,

    1. European Molecular Biology Laboratory, Meyerhofstrasse 1, Heidelberg D-69117, Germany;
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  • T. G. Loukeris,

    1. Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, Vassilika Vouton, 711 10 Heraklion, Crete, Greece;
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  • M. J. I. Paine

    1. Biomedical Research Centre, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK
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Dr Mark J. I. Paine, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK. Tel. +44(0)151 7089393; Fax. +44(0)151 7053370; email: m.j.paine@liverpool.ac.uk

Abstract

We describe an in vivo model for investigation of detoxification mechanisms of the mosquito Anopheles gambiae, important for the development of malaria control programmes. Cytochrome P450s are involved in metabolic insecticide resistance and require NADPH cytochrome P450 reductase (CPR) to function. Here we demonstrate that the major sites of adult mosquito CPR expression are oenocytes, mid-gut epithelia and head appendages. High CPR expression was also evident in Drosophila oenocytes indicating a general functional role in these insect cells. RNAi mediated knockdown drastically reduced CPR expression in oenocytes, and to a lesser extent in mid-gut epithelia; the head was unaffected. These flies showed enhanced sensitivity to permethrin, demonstrating a key role for abdominal/mid-gut P450s in pyrethroid metabolism, aiding the development of insecticides.

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