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We use an ovine model of CF to investigate the in utero origins of CF disease since the sheep closely mirrors critical aspects of human development. Wildtype (WT) and <jats:italic>CFTR<\/jats:italic> <jats:sup>\u2010\/\u2010<\/jats:sup> sheep tissues were collected at 50, 65, 80, 100, and 120\u2009days of gestation and term (147\u2009days) and used for histological, electrophysiological, and molecular analysis. Histological abnormalities are evident in <jats:italic>CFTR\u2010\/\u2010<\/jats:italic> <jats:sup>\u2010\/\u2010<\/jats:sup> \u00a0animals by 80\u2009days of gestation, equivalent to 21\u2009weeks in humans. Acinar and ductal dilation, mucus obstruction, and fibrosis are observed in the pancreas; biliary fibrosis, cholestasis, and gallbladder hypoplasia in the liver; and intestinal meconium obstruction, as seen at birth in all large animal models of CF. Concurrently, cystic fibrosis transmembrane conductance regulator (CFTR)\u2010dependent short circuit current is present in WT tracheal epithelium by 80\u2009days gestation and is absent from <jats:italic>CFTR<\/jats:italic> <jats:sup>\u2010\/\u2010<\/jats:sup> tissues. Transcriptomic profiles of tracheal tissues confirm the early expression of <jats:italic>CFTR<\/jats:italic> and suggest that its loss does not globally impair tracheal differentiation.<\/jats:p>","DOI":"10.1096\/fba.2022-00085","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T22:49:21Z","timestamp":1666046961000},"page":"13-26","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Early developmental phenotypes in the cystic fibrosis sheep model"],"prefix":"10.1096","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9611-1316","authenticated-orcid":false,"given":"Arnaud J.","family":"Van Wettere","sequence":"first","affiliation":[{"name":"Department of Animal, Dairy and Veterinary Sciences Utah State University  Logan Utah USA"},{"name":"School of Veterinary Medicine Utah State University  Logan Utah 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