{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:35:00Z","timestamp":1790253300448,"version":"4.1.0"},"reference-count":84,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2018,7,13]],"date-time":"2018-07-13T00:00:00Z","timestamp":1531440000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,7,13]],"date-time":"2018-07-13T00:00:00Z","timestamp":1531440000000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,7,13]],"date-time":"2018-07-13T00:00:00Z","timestamp":1531440000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["CIHR MOP-97954"],"award-info":[{"award-number":["CIHR MOP-97954"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["CIHR GPG-102171"],"award-info":[{"award-number":["CIHR GPG-102171"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000082","name":"Cystic Fibrosis Canada","doi-asserted-by":"publisher","award":["CFC-1"],"award-info":[{"award-number":["CFC-1"]}],"id":[{"id":"10.13039\/501100000082","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    The severity of intestinal disease associated with Cystic Fibrosis (CF) is variable in the patient population and this variability is partially conferred by the influence of modifier genes. Genome-wide association studies have identified\n                    <jats:italic>SLC6A14,<\/jats:italic>\n                    an electrogenic amino acid transporter, as a genetic modifier of CF-associated meconium ileus. The purpose of the current work was to determine the biological role of\n                    <jats:italic>Slc6a14,<\/jats:italic>\n                    by disrupting its expression in CF mice bearing the major mutation, F508del. We found that disruption of\n                    <jats:italic>Slc6a14<\/jats:italic>\n                    worsened the intestinal fluid secretion defect, characteristic of these mice. In vitro studies of mouse intestinal organoids revealed that exacerbation of the primary defect was associated with reduced arginine uptake across the apical membrane, with aberrant nitric oxide and cyclic GMP-mediated regulation of the major CF-causing mutant protein. Together, these studies highlight the role of this apical transporter in modifying cellular nitric oxide levels, residual function of the major CF mutant and potentially, its promise as a therapeutic target.\n                  <\/jats:p>","DOI":"10.7554\/elife.37963","type":"journal-article","created":{"date-parts":[[2018,7,13]],"date-time":"2018-07-13T08:02:40Z","timestamp":1531468960000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.37963","source":"Crossref","is-referenced-by-count":36,"title":["SLC6A14, an amino acid transporter, modifies the primary CF defect in fluid secretion"],"prefix":"10.7554","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5800-6945","authenticated-orcid":true,"given":"Saumel","family":"Ahmadi","sequence":"first","affiliation":[{"name":"Department of Physiology, University of Toronto, Toronto, Canada"},{"name":"Programme in Molecular Medicine, Research Institute, Hospital for Sick Children, Toronto, 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