{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:27:05Z","timestamp":1790796425030,"version":"4.1.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T00:00:00Z","timestamp":1699315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Neuropeptide Y receptor Y2 (<jats:italic>npy2r<\/jats:italic>) is an important receptor gene involved in anxiety and feeding regulation in mammals. Since NPY receptors have different receptor gene deletions in mammals and teleost fish, it is not clear whether <jats:italic>npy2r<\/jats:italic> has the similar function in fish as in mammals. In this study, we used the CRISPR\/Cas9 system to establish <jats:italic>npy2r<\/jats:italic>-deficient medaka (<jats:italic>Oryzias latipes<\/jats:italic>). Unexpectedly, the deletion of <jats:italic>npy2r<\/jats:italic> resulted in the <jats:italic>npy2r<\/jats:italic><jats:sup><jats:italic>+\/\u2212<\/jats:italic><\/jats:sup> medaka were all-male, therefore, <jats:italic>npy2r<\/jats:italic> homozygous mutant lines could not be established. The deletion of <jats:italic>npy2r<\/jats:italic> increased the food intake in medaka, and the expression levels of appetite stimulating genes (<jats:italic>agrp<\/jats:italic>, <jats:italic>npy<\/jats:italic>) increased significantly, while the expression levels of anorexia factors (<jats:italic>cck<\/jats:italic>, <jats:italic>pomc<\/jats:italic>) decreased significantly. Moreover, the absence of <jats:italic>npy2r<\/jats:italic> significantly increased the total length and body weight of medaka. The mirror test and open field test showed that <jats:italic>npy2r<\/jats:italic><jats:sup><jats:italic>+\/\u2212<\/jats:italic><\/jats:sup> medaka improved sociability and reduced anxiety-like behavior, qRT-PCR analysis showed that the expression levels of anxiety related genes (<jats:italic>th1<\/jats:italic>, <jats:italic>th2<\/jats:italic>, <jats:italic>gr1<\/jats:italic>, <jats:italic>gr2<\/jats:italic>, and <jats:italic>mr<\/jats:italic>) in <jats:italic>npy2r<\/jats:italic><jats:sup><jats:italic>+\/\u2212<\/jats:italic><\/jats:sup> medaka were significantly decreased. So far, this is the first <jats:italic>npy2r<\/jats:italic> gene knockout model established in fish and demonstrates that <jats:italic>npy2r<\/jats:italic> plays an important role in the regulation of reproduction, feeding and anxiety in fish.<\/jats:p>","DOI":"10.3389\/fcell.2023.1273006","type":"journal-article","created":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T07:58:36Z","timestamp":1699343916000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Neuropeptide Y receptor Y2 (npy2r) deficiency reduces anxiety and increases food intake in Japanese medaka (Oryzias latipes)"],"prefix":"10.3389","volume":"11","author":[{"given":"Ke","family":"Lu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodan","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuling","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu-Fang","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.bbr.2016.01.050","article-title":"Chronic fluoxetine treatment induces anxiolytic responses and altered social behaviors in medaka, Oryzias latipes","volume":"303","author":"Ansai","year":"2016","journal-title":"Behav. 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