{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T20:25:06Z","timestamp":1792959906223,"version":"4.5.0"},"reference-count":40,"publisher":"American Society for Clinical Investigation","issue":"19","funder":[{"DOI":"10.13039\/100007199","name":"Utah Agricultural Experiment Station","doi-asserted-by":"crossref","award":["UTAO1328"],"award-info":[{"award-number":["UTAO1328"]}],"id":[{"id":"10.13039\/100007199","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"crossref","award":["Award# POLEJA17XX0"],"award-info":[{"award-number":["Award# POLEJA17XX0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,10,4]]},"abstract":"<jats:p>\n                    Cystic fibrosis (CF) is a genetic disease caused by mutations in the CF transmembrane conductance regulator (\n                    <jats:italic>CFTR<\/jats:italic>\n                    ) gene. The major cause of limited life span in CF patients is progressive lung disease. CF models have been generated in 4 species (mice, rats, ferrets, and pigs) to enhance our understanding of the CF pathogenesis. Sheep may be a particularly relevant animal to model CF in humans due to the similarities in lung anatomy and development in the two species. Here, we describe the generation of a sheep model for CF using CRISPR\/Cas9 genome editing and somatic cell nuclear transfer (SCNT) techniques. We generated cells with\n                    <jats:italic>CFTR<\/jats:italic>\n                    gene disruption and used them for production of\n                    <jats:italic>\n                      CFTR\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    and\n                    <jats:italic>\n                      CFTR\n                      <jats:sup>+\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    lambs. The newborn\n                    <jats:italic>\n                      CFTR\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    sheep developed severe disease consistent with CF pathology in humans. Of particular relevance were pancreatic fibrosis, intestinal obstruction, and absence of the vas deferens. Also, substantial liver and gallbladder disease may reflect CF liver disease that is evident in humans. The phenotype of\n                    <jats:italic>\n                      CFTR\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    sheep suggests this large animal model will be a useful resource to advance the development of new CF therapeutics. Moreover, the generation of specific human CF disease\u2013associated mutations in sheep may advance personalized medicine for this common genetic disorder.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.123529","type":"journal-article","created":{"date-parts":[[2018,10,3]],"date-time":"2018-10-03T11:01:24Z","timestamp":1538564484000},"source":"Crossref","is-referenced-by-count":123,"title":["A sheep model of cystic fibrosis generated by CRISPR\/Cas9 disruption of the CFTR gene"],"prefix":"10.1172","volume":"3","author":[{"given":"Zhiqiang","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, Utah, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iuri Viotti","family":"Perisse","sequence":"additional","affiliation":[{"name":"Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, Utah, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calvin U.","family":"Cotton","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, Physiology and Biophysics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misha","family":"Regouski","sequence":"additional","affiliation":[{"name":"Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, Utah, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinggang","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, Utah, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaim","family":"Domb","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, Physiology and Biophysics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9611-1316","authenticated-orcid":true,"given":"Arnaud J.","family":"Van Wettere","sequence":"additional","affiliation":[{"name":"Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, Utah, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongde","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, Utah, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6541-2546","authenticated-orcid":true,"given":"Ann","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth 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