Cited by 474Neurobiology and Insect Physiology ResearchInsect Pheromone Research and ControlInsect Pest Control Strategies

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

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DeGennaro, Matthew, McBride, Carolyn S., Seeholzer, Laura, Nakagawa, Takao, Dennis, Emily J., Goldman, Chloe, Jasinskiene, Nijole, James, Anthony A., Vosshall, Leslie B.·2013·Nature

DOI 10.1038/nature12206PMC PMC3696029

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Abstract

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 fever. 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 hosts. Insects sense odours via several chemosensory receptor families, including the odorant receptors (ORs), membrane proteins that form heteromeric odour-gated ion channels 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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Additional file 3 of Genome-wide identification and expression profiling of odorant receptor genes in the malaria vector Anopheles sinensis
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Additional file 6 of Metamorphic development of the olfactory system in the red flour beetle (Tribolium castaneum, Herbst)
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Additional file 6 of Genome-wide identification and expression profiling of odorant receptor genes in the malaria vector Anopheles sinensis
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Additional file 12 of Genome-wide identification and expression profiling of odorant receptor genes in the malaria vector Anopheles sinensis
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Additional file 7 of Metamorphic development of the olfactory system in the red flour beetle (Tribolium castaneum, Herbst)
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Additional file 9 of Genome-wide identification and expression profiling of odorant receptor genes in the malaria vector Anopheles sinensis
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Additional file 13 of Genome-wide identification and expression profiling of odorant receptor genes in the malaria vector Anopheles sinensis
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Additional file 2 of Genome-wide identification and expression profiling of odorant receptor genes in the malaria vector Anopheles sinensis
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Additional file 1 of Species and sex-specific chemosensory gene expression in Anopheles coluzzii and An. quadriannulatus antennae
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Additional file 5 of Genome-wide identification and expression profiling of odorant receptor genes in the malaria vector Anopheles sinensis
He, Z., Yu, Z., He, X., Hao, Y., Qiao, L., Luo, S., Zhang, J., & Chen, B. (2022) · Figshare · doi:10.6084/m9.figshare.19642715
Additional file 2 of A cilia-bound unconventional secretory pathway for Drosophila odorant receptors
Dzaki, N., & Alenius, M. (2024) · Figshare · doi:10.6084/m9.figshare.25596564
Additional file 2 of Species and sex-specific chemosensory gene expression in Anopheles coluzzii and An. quadriannulatus antennae
Athrey, G., Popkin-Hall, Z. R., Cosme, L. V., Takken, W., & Slotman, M. A. (2020) · Figshare · doi:10.6084/m9.figshare.12177642
Additional file 3 of Species and sex-specific chemosensory gene expression in Anopheles coluzzii and An. quadriannulatus antennae
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Additional file 8 of Genome-wide identification and expression profiling of odorant receptor genes in the malaria vector Anopheles sinensis
He, Z., Yu, Z., He, X., Hao, Y., Qiao, L., Luo, S., Zhang, J., & Chen, B. (2022) · Figshare · doi:10.6084/m9.figshare.19642724
Additional file 3 of A cilia-bound unconventional secretory pathway for Drosophila odorant receptors
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Additional file 2 of Metamorphic development of the olfactory system in the red flour beetle (Tribolium castaneum, Herbst)
Trebels, B., Dippel, S., Goetz, B., Graebner, M., Hofmann, C., Hofmann, F., Schmid, F.-R., Uhl, M., Vuong, M.-P., Weber, V., et al. (2021) · Figshare · doi:10.6084/m9.figshare.15086156
Additional file 5 of Metamorphic development of the olfactory system in the red flour beetle (Tribolium castaneum, Herbst)
Trebels, B., Dippel, S., Goetz, B., Graebner, M., Hofmann, C., Hofmann, F., Schmid, F.-R., Uhl, M., Vuong, M.-P., Weber, V., et al. (2021) · Figshare · doi:10.6084/m9.figshare.15086159
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Authors: DeGennaro, M., McBride, C. S., Seeholzer, L., Nakagawa, T., Dennis, E. J., Goldman, C., Jasinskiene, N., James, A. A., & Vosshall, L. B.
Affiliations: Howard Hughes Medical Institute (US)
Rockefeller University (US)
University of California, Irvine (US)
Corresponding author: Vosshall, Leslie B.
ORCID: DeGennaro, Matthew
McBride, Carolyn S.
Seeholzer, Laura
Dennis, Emily J.
Jasinskiene, Nijole
James, Anthony A.
Vosshall, Leslie B.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2013-05-29
Volume: 498
Issue: 7455
Pages: 487-491
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature12206
PMC: PMC3696029
OpenAlex: W2021253771
Cited by: 473
References: 39
Citations by year: 2026: 22 · 2025: 32 · 2024: 36 · 2023: 39 · 2022: 62 · 2021: 47 · 2020: 45 · 2019: 41 · 2018: 30 · 2017: 21 · 2016: 31 · 2015: 26 · 2014: 27 · 2013: 14
FWCI: 16.03
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders: Howard Hughes Medical Institute
National Institute on Deafness and Other Communication Disorders (DC012069, K99DC012069, R00DC012069)
National Institute of Allergy and Infectious Diseases (R37AI029746, R01AI029746, AI29746)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
Life Sciences › Agricultural and Biological Sciences › Insect Science › Insect Pheromone Research and Control
Life Sciences › Agricultural and Biological Sciences › Plant Science › Insect Pest Control Strategies
Keywords: Orco, mosquito host preference, Aedes aegypti, Anopheles gambiae, olfactory receptors, olfactory sensory neurons, mosquito olfaction, host-seeking behavior, gene targeting, zinc finger nucleases
MeSH terms: Aedes, Amino Acid Sequence, Animals, Base Sequence, DEET, Drug Resistance, Female, Honey, Humans, Insect Repellents, Male, Molecular Sequence Data, Mutation, Neurons, Odorants, Olfactory Pathways, Volatilization, Mutagenesis, Site-Directed, Genes, Insect, Host Specificity

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

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