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Mutations in the nicotinic acetylcholine receptor (nAChR) \u03b16 subunit have been identified that are associated with levels of spinosad resistance, but the molecular characterization of the nAChR gene family and a causative association between nAChR \u03b16 and resistance to spinosad in <jats:italic>Aedes aegypti<\/jats:italic>, a primary vector of many arboviruses, have not yet been reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>In this study, we identified 10 candidate nAChR subunits in <jats:italic>Ae. Aegypti<\/jats:italic>, nAChR\u03b11\u2013\u03b19 and nAChR\u03b21, showing similarly orthologous relationships with <jats:italic>Anopheles gambiae<\/jats:italic>. With the application of the CRISPR\/Cas9 genome editing system, we introduced a 32\u2010bp deletion at the 5\u2032 end of the <jats:italic>Aae\u03b16<\/jats:italic> (<jats:italic>Ae. aegypti<\/jats:italic> nAChR \u03b16) gene in a homozygous mutant strain (Aae\u03b16\u2010KO). The mutation produced two successive pre\u2010mature stop codons, resulting in loss of function in the target receptor. The Aae\u03b16\u2010KO mutant strain exhibited a 320\u2010fold level of resistance to spinosad compared with wildtype. A recessive mode of inheritance for spinosad resistance was found in the Aae\u03b16\u2010KO strain.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>CRISPR\/Cas9 introduced truncated Aae\u03b16 receptor in <jats:italic>Ae. aegypti<\/jats:italic> resulted in an increased level of resistance to spinosad, suggesting that the conserved nAChR \u03b16 subunit is the target for spinosad insecticide. \u00a9 2020 Society of Chemical Industry<\/jats:p><\/jats:sec>","DOI":"10.1002\/ps.6183","type":"journal-article","created":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T13:25:01Z","timestamp":1605619501000},"page":"1633-1641","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Identification of the <scp><i>Aedes aegypti<\/i> nAChR<\/scp> gene family and molecular target of spinosad"],"prefix":"10.1002","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8470-5419","authenticated-orcid":false,"given":"Jianqiang","family":"Lan","sequence":"first","affiliation":[{"name":"Laboratory of Tropical Veterinary Medicine and Vector Biology School of Life and Pharmaceutical Sciences, Hainan University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihe","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Tropical Veterinary Medicine and Vector Biology School of Life and Pharmaceutical Sciences, Hainan University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohui","family":"Chen","sequence":"additional","affiliation":[{"name":"Laboratory of Tropical Veterinary Medicine and Vector Biology School of Life and Pharmaceutical Sciences, Hainan University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Laboratory of Tropical Veterinary Medicine and Vector Biology School of Life and Pharmaceutical Sciences, Hainan University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguo","family":"Zhao","sequence":"additional","affiliation":[{"name":"Laboratory of Tropical Veterinary Medicine and Vector Biology School of Life and Pharmaceutical Sciences, Hainan University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingfeng","family":"Guan","sequence":"additional","affiliation":[{"name":"Laboratory of Tropical Veterinary Medicine and Vector Biology School of Life and Pharmaceutical Sciences, Hainan University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenghong","family":"Liao","sequence":"additional","affiliation":[{"name":"Laboratory of Tropical Veterinary Medicine and Vector Biology School of Life and Pharmaceutical Sciences, Hainan University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nannan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Entomology and Plant Pathology Auburn University  Auburn AL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6245-5252","authenticated-orcid":false,"given":"Qian","family":"Han","sequence":"additional","affiliation":[{"name":"Laboratory of Tropical Veterinary Medicine and Vector Biology School of Life and Pharmaceutical Sciences, Hainan University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,12,10]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"WHO Vector\u2010Borne Diseases 2020. 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