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To investigate the role and mechanism of copper in the sheep pancreas, we first established sheep pancreatic duct organoids (sPDOs). We found that an appropriate amount of copper benefited the formation and growth of sPDOs, whereas excess or deficient copper damaged sPDOs. We found that the proliferation-stimulating effect of copper was related to the copper chaperone antioxidant protein 1 (ATOX1)-dependent activation of MEK-ERK1\/2 signaling. Atox1 knockdown suppressed the cell proliferation of sPDOs, even in the presence of the MEK activator. These results indicate that moderate concentrations of copper promote sPDO growth through ATOX1-regulated cell proliferation by activation of MEK-ERK. Moreover, our study indicates that organoids may be a useful model to study organ growth mechanisms in livestock. <\/jats:p>","DOI":"10.1152\/ajpcell.00509.2019","type":"journal-article","created":{"date-parts":[[2020,3,4]],"date-time":"2020-03-04T18:50:58Z","timestamp":1583347858000},"page":"C806-C816","source":"Crossref","is-referenced-by-count":18,"title":["Copper promotes sheep pancreatic duct organoid growth by activation of an antioxidant protein 1-dependent MEK-ERK pathway"],"prefix":"10.1152","volume":"318","author":[{"given":"Miao","family":"Liu","sequence":"first","affiliation":[{"name":"Animal Development Biology Laboratory, College of Life Science, Northeast Forestry University, Harbin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Yu","sequence":"additional","affiliation":[{"name":"Animal Development Biology Laboratory, College of Life Science, Northeast Forestry University, Harbin, 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