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orco mutant mosquitoes lose strong preference for humans and are not repelled by volatile DEET


Female mosquitoes of some species are generalists and will blood-feed on a variety of vertebrate hosts, whereas others display marked host preference. Anopheles gambiae and Aedes aegypti have evolved a strong preference for humans, making them dangerously efficient vectors of malaria and Dengue haemorrhagic fever1. Specific host odours probably drive this strong preference because other attractive cues, including body heat and exhaled carbon dioxide (CO2), are common to all warm-blooded hosts2,3. Insects sense odours via several chemosensory receptor families, including the odorant receptors (ORs), membrane proteins that form heteromeric odour-gated ion channels4,5 comprising a variable ligand-selective subunit and an obligate co-receptor called Orco (ref. 6). Here we use zinc-finger nucleases to generate targeted mutations in the orco gene of A. aegypti to examine the contribution of Orco and the odorant receptor pathway to mosquito host selection and sensitivity to the insect repellent DEET (N,N-diethyl-meta-toluamide). orco mutant olfactory sensory neurons have greatly reduced spontaneous activity and lack odour-evoked responses. Behaviourally, orco mutant mosquitoes have severely reduced attraction to honey, an odour cue related to floral nectar, and do not respond to human scent in the absence of CO2. However, in the presence of CO2, female orco mutant mosquitoes retain strong attraction to both human and animal hosts, but no longer strongly prefer humans. orco mutant females are attracted to human hosts even in the presence of DEET, but are repelled upon contact, indicating that olfactory- and contact-mediated effects of DEET are mechanistically distinct. We conclude that the odorant receptor pathway is crucial for an anthropophilic vector mosquito to discriminate human from non-human hosts and to be effectively repelled by volatile DEET.

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Figure 1: Targeted mutagenesis of orco in A. aegypti.
Figure 2: Reduced spontaneous activity and loss of odour-evoked responses in orco mutant olfactory neurons.
Figure 3: Disruption of honey odour detection in orco mutants.
Figure 4: Disruption of host detection and discrimination in orco mutants.
Figure 5: Female orco mutants are insensitive to volatile DEET but are repelled on contact.


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We thank K. J. Lee and members of the Vosshall lab for comments on the manuscript. F. Urnov of Sangamo BioSciences suggested the experiments in Supplementary Fig. 1. We thank C. McMeniman for initiating the A. aegypti GFP ZFN disruption project together with M.D. and for establishing mosquito microinjection at Genetic Services Inc. S. Dewell of the Rockefeller University Genomics Resource Center provided bioinformatic assistance. W. Takken and N. Verhulst suggested the use of nylon stockings in Figs 4 and 5. Román Corfas provided advice on imaging in Fig. 5b. This work was funded in part by a grant to R. Axel and L.B.V. from the Foundation for the National Institutes of Health through the Grand Challenges in Global Health Initiative. This work was supported in part by grants from the National Institutes of Health to C.S.M. (DC012069) and N.J. and A.A.J. (AI29746). L.B.V. is an investigator of the Howard Hughes Medical Institute.

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Authors and Affiliations



M.D. carried out the experiments in Fig. 1 and Supplementary Fig. 1 and Supplementary Fig 2b, c. E.J.D. carried out the experiments in Supplementary Fig. 2a. N.J. generated the GFP transgenic A. aegypti and injected the GFP ZFN for Supplementary Fig. 1 and was supervised by A.A.J. T.N. carried out the experiments in Fig. 2. C.G. reared mosquitoes and genotyped orco mutants. C.S.M. developed the assays used in Figs 3 and 4 with M.D. and L.S. L.S., M.D. and C.S.M. carried out the experiments in Figs 3 and 4. L.S., E.J.D. and M.D. developed and carried out the assays in Fig 5. M.D., C.S.M. and L.B.V. wrote the paper.

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Correspondence to Leslie B. Vosshall.

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Supplementary information

Supplementary Information

This file contains Supplementary Figures 1-3, Supplementary Methods and additional references. (PDF 1939 kb)

Aedes aegypti orco mutants are attracted to a DEET-treated human arm

Time-lapse 4 minute video of the human host proximity assay using a human arm treated with 10% DEET shown at 16x speed (see Fig. 5b). The video shows an introductory cartoon highlighting the human arm and the cage screen followed by a side-by-side view of one trial each of wild-type (left) and orco2/5 mutant (right) female mosquitoes. Video images were recorded in the same manner as for the experiments in Figure 5b, except at a rate of 1 frame per second. (MOV 14207 kb)

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DeGennaro, M., McBride, C., Seeholzer, L. et al. orco mutant mosquitoes lose strong preference for humans and are not repelled by volatile DEET. Nature 498, 487–491 (2013).

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