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Unlike other MCRs, the melanocortin 2 receptor (MC2R) is exclusively activated by ACTH; however, its role in pigmentation remains unclear. Using CRISPR\/Cas9-generated\n                    <jats:italic>mc2r<\/jats:italic>\n                    knockout zebrafish, we demonstrated that the loss of\n                    <jats:italic>mc2r<\/jats:italic>\n                    in zebrafish results in impaired interrenal steroidogenesis and pronounced hyperpigmentation characterized by an increased number of melanophores and xanthophores while preserving normal patterning. Transcriptomic analyses revealed the upregulation of genes involved in melanosome formation, melanin synthesis, lipid metabolism, and carotenoid accumulation. These findings demonstrate that, in addition to controlling steroidogenesis,\n                    <jats:italic>mc2r<\/jats:italic>\n                    plays a key role in pigment cell development and metabolic regulation.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-37998-7","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T06:50:52Z","timestamp":1770187852000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Loss-of-function mutations in the melanocortin-2-receptor (mc2r) lead to skin hyperpigmentation in teleost fish"],"prefix":"10.1038","volume":"16","author":[{"given":"Elisa","family":"Barreiro-Doc\u00edo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Guerrero-Pe\u00f1a","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priyanka","family":"Soni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"M\u00e9ndez-Mart\u00ednez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"Costas-Prado","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Victoria","family":"Alvarado","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Antonio","family":"V\u00e1zquez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Llu\u00eds","family":"Tort","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Miguel","family":"Cerd\u00e1-Reverter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josep","family":"Rotllant","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"37998_CR1","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1111\/j.1751-1097.2007.00226.x","volume":"84","author":"M Brenner","year":"2008","unstructured":"Brenner, M. & Hearing, V. 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