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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2019,10,22]]},"abstract":"<jats:p>\n                    The yellow fever mosquito,\n                    <jats:italic>Aedes aegypti<\/jats:italic>\n                    , vectors human pathogens. Juvenile hormones (JH) control almost every aspect of an insect\u2019s life, and JH analogs are currently used to control mosquito larvae. Since RNA interference does not work efficiently during the larval stages of this insect, JH regulation of larval development and mode of action of JH analogs are not well studied. To overcome this limitation, we used a multiple single guide RNA-based CRISPR\/Cas9 genome-editing method to knockout the\n                    <jats:italic>methoprene-tolerant<\/jats:italic>\n                    (\n                    <jats:italic>Met<\/jats:italic>\n                    ) gene coding for a JH receptor. The\n                    <jats:italic>Met<\/jats:italic>\n                    knockout larvae exhibited a black larval phenotype during the L3 (third instar larvae) and L4 (fourth instar larvae) stages and died before pupation. However,\n                    <jats:italic>Met<\/jats:italic>\n                    knockout did not affect embryonic development or the L1 and L2 stages. Microscopy studies revealed the precocious synthesis of a dark pupal cuticle during the L3 and L4 stages. Gene expression analysis showed that\n                    <jats:italic>Kr\u00fcppel homolog 1<\/jats:italic>\n                    , a key transcription factor in JH action, was down-regulated, but genes coding for proteins involved in melanization, pupal and adult cuticle synthesis, and blood meal digestion in adults were up-regulated in L4\n                    <jats:italic>Met<\/jats:italic>\n                    mutants. These data suggest that, during the L3 and L4 stages,\n                    <jats:italic>Met<\/jats:italic>\n                    mediates JH suppression of pupal\/adult genes involved in the synthesis and melanization of the cuticle and blood meal digestion. These results help to advance our knowledge of JH regulation of larval development and the mode of action of JH analogs in\n                    <jats:italic>Ae. aegypti<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1073\/pnas.1905729116","type":"journal-article","created":{"date-parts":[[2019,9,30]],"date-time":"2019-09-30T22:27:57Z","timestamp":1569882477000},"page":"21501-21507","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":63,"title":["Knockout of juvenile hormone receptor, Methoprene-tolerant, induces black larval phenotype in the yellow fever mosquito,\n                    <i>Aedes aegypti<\/i>"],"prefix":"10.1073","volume":"116","author":[{"given":"Guan-Heng","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Entomology, College of Agriculture, Food and Environment, University of Kentucky, Lexington, KY 40546;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaoyu","family":"Jiao","sequence":"additional","affiliation":[{"name":"Department of Entomology, College of Agriculture, Food and Environment, University of Kentucky, Lexington, KY 40546;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shankar C. 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