{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T18:22:37Z","timestamp":1780597357224,"version":"3.54.1"},"reference-count":42,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32160777"],"award-info":[{"award-number":["32160777"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2025,7,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Sheep coat color is an important phenotypic trait that influences consumer preferences and breeding. Although the\n                    <jats:italic>Agouti<\/jats:italic>\n                    Signaling Protein (\n                    <jats:italic>ASIP<\/jats:italic>\n                    ) gene has been linked to pigmentation, the mechanisms underlying its function remain unclear. In a previous study, we generated\n                    <jats:italic>ASIP<\/jats:italic>\n                    gene\u2010edited fine\u2010wool sheep (F0) with diverse coat colors using CRISPR\/Cas9. Building on this foundation, the present study investigates coat color variation in 33 F1 offspring produced by mating F0 gene\u2010edited rams with either F0 gene\u2010edited ewes or wild\u2010type white ewes. Comprehensive genotyping identified two inherited\n                    <jats:italic>ASIP<\/jats:italic>\n                    mutations\u2014a 4\u2010bp deletion and a 27\u2010bp deletion with a 1\u2010bp insertion\u2014alongside natural variants (D\n                    <jats:sub>5<\/jats:sub>\n                    , D\n                    <jats:sub>9<\/jats:sub>\n                    ) and copy number variation. These genetic differences were associated with a wide range of coat color phenotypes in the F1 population. To explore the underlying mechanisms, we conducted histological analyses (H&amp;E staining), immunohistochemistry, melanin content quantification, qRT\u2010PCR, and Western blotting. Results showed that dark\u2010coated individuals exhibited reduced\n                    <jats:italic>ASIP<\/jats:italic>\n                    expression and elevated levels of\n                    <jats:italic>TYR<\/jats:italic>\n                    and\n                    <jats:italic>TYRP1<\/jats:italic>\n                    , consistent with increased eumelanin synthesis. In contrast, white\u2010coated sheep showed higher\n                    <jats:italic>ASIP<\/jats:italic>\n                    expression and lower levels of melanogenic enzymes. Our findings provide functional validation that\n                    <jats:italic>ASIP<\/jats:italic>\n                    is a central regulator of pigmentation in sheep and reveal how the interplay between gene editing, natural mutations, and gene dosage contributes to diverse coat color outcomes. This work establishes a valuable model for dissecting coat color genetics and offers a molecular framework for future breeding strategies aimed at wool color diversification and economic trait improvement in fine\u2010wool sheep.\n                  <\/jats:p>","DOI":"10.1096\/fj.202500355r","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T14:29:18Z","timestamp":1752762558000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Insights Into Coat Color Variation: Unraveling the Role of\n                    <scp>\n                      <i>ASIP<\/i>\n                    <\/scp>\n                    by Gene Editing in Fine\u2010Wool Sheep"],"prefix":"10.1096","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6277-6951","authenticated-orcid":false,"given":"Xue\u2010mei","family":"Zhang","sequence":"first","affiliation":[{"name":"Key Laboratory of Genetics, Breeding and 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