biostudies-literatureLi RBeijing Natural Science Foundation for Young ScienceBeijing Key Laboratory of Fisheries BiotechnologyNational Freshwater Aquatic Germplasm Resource BankNational Engineering Research Center for Freshwaters (Beijing)National Natural Science Foundation of China, Youth Fund Project10625https://www.ebi.ac.uk/biostudies/studies/S-EPMC12608239biostudies-literatureUnknown26(21)After intensive artificial selection, the development of celestial eyes in goldfish involves the eyeballs protuberating and turning upwards. Thus, the celestial eye goldfish is an excellent model for both evolutionary and human ocular disease studies. Here, two mapping populations of goldfish with segregating eye phenotypes in the offspring were constructed. Through whole-genome sequencing and RNA-seq for eyeball samples, a premature stop codon in Exon 38 of the <i>LRP2</i> gene was identified as the top candidate mutation for the celestial eye in goldfish. Fatty acid metabolism and epidermal cells, especially keratocyte-related functions, were inhibited in the eyeballs of celestial eye goldfish, while inflammatory reactions and extracellular matrix secretions were stimulated. These resultInternational journal of molecular sciencesIndependent Mutations in the &lt;i&gt;LRP2&lt;/i&gt; Gene Mediating Telescope Eyes and Celestial Eyes in Goldfish.PMC1260823932302996FGRC: 18537PT2024-206234045PT2024-19Li JLi RZhang BSun YfalseIndependent Mutations in the &lt;i&gt;LRP2&lt;/i&gt; Gene Mediating Telescope Eyes and Celestial Eyes in Goldfish.After intensive artificial selection, the development of celestial eyes in goldfish involves the eyeballs protuberating and turning upwards. Thus, the celestial eye goldfish is an excellent model for both evolutionary and human ocular disease studies. Here, two mapping populations of goldfish with segregating eye phenotypes in the offspring were constructed. Through whole-genome sequencing and RNA-seq for eyeball samples, a premature stop codon in Exon 38 of the <i>LRP2</i> gene was identified as the top candidate mutation for the celestial eye in goldfish. Fatty acid metabolism and epidermal cells, especially keratocyte-related functions, were inhibited in the eyeballs of celestial eye goldfish, while inflammatory reactions and extracellular matrix secretions were stimulated. These result2025-01-01T00:00:00Z2025 Oct2026-05-17T03:15:57.245Z2026-05-17T03:07:41.821ZS-EPMC126082394122666110.3390/ijms262110625