{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T11:03:22Z","timestamp":1784027002472,"version":"3.55.0"},"reference-count":71,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,12,8]],"date-time":"2021-12-08T00:00:00Z","timestamp":1638921600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Dysfunction of the epithelial anion channel cystic fibrosis transmembrane conductance regulator (CFTR) causes a wide spectrum of disease, including cystic fibrosis (CF) and CFTR\u2010related diseases (CFTR\u2010RDs). Here, we investigate genotype\u2013phenotype\u2013CFTR function relationships using human nasal epithelial (hNE) cells from a small cohort of non\u2010CF subjects and individuals with CF and CFTR\u2010RDs and genotypes associated with either residual or minimal CFTR function using electrophysiological techniques. Collected hNE cells were either studied directly with the whole\u2010cell patch\u2010clamp technique or grown as primary cultures at an air\u2013liquid interface after conditional reprogramming. The properties of cAMP\u2010activated whole\u2010cell Cl<jats:sup>\u2212<\/jats:sup> currents in freshly isolated hNE cells identified them as CFTR\u2010mediated. Their magnitude varied between hNE cells from individuals within the same genotype and decreased in the rank order: non\u2010CF &gt; CFTR residual function &gt; CFTR minimal function. CFTR\u2010mediated whole\u2010cell Cl<jats:sup>\u2212<\/jats:sup> currents in hNE cells isolated from fully differentiated primary cultures were identical to those in freshly isolated hNE cells in both magnitude and behaviour, demonstrating that conditional reprogramming culture is without effect on CFTR expression and function. For the cohort of subjects studied, CFTR\u2010mediated whole\u2010cell Cl<jats:sup>\u2212<\/jats:sup> currents in hNE cells correlated well with CFTR\u2010mediated transepithelial Cl<jats:sup>\u2212<\/jats:sup> currents measured <jats:italic>in vitro<\/jats:italic> with the Ussing chamber technique, but not with those determined <jats:italic>in vivo<\/jats:italic> with the nasal potential difference assay. Nevertheless, they did correlate with the sweat Cl<jats:sup>\u2212<\/jats:sup> concentration of study subjects. Thus, this study highlights the complexity of genotype\u2013phenotype\u2013CFTR function relationships, but emphasises the value of conditionally reprogrammed hNE cells in CFTR research and therapeutic testing.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp14883-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>The genetic disease cystic fibrosis is caused by pathogenic variants in the cystic fibrosis transmembrane conductance regulator (CFTR), an ion channel, which controls anion flow across epithelia lining ducts and tubes in the body.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This study investigated CFTR function in nasal epithelial cells from people with cystic fibrosis and CFTR variants with a range of disease severity.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>CFTR function varied widely in nasal epithelial cells depending on the identity of CFTR variants, but was unaffected by conditional reprogramming culture, a cell culture technique used to grow large numbers of patient\u2010derived cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Assessment of CFTR function <jats:italic>in vitro<\/jats:italic> in nasal epithelial cells and epithelia, and <jats:italic>in vivo<\/jats:italic> in the nasal epithelium and sweat gland highlights the complexity of genotype\u2013phenotype\u2013CFTR function relationships.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp282143","type":"journal-article","created":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T11:29:38Z","timestamp":1636630178000},"page":"1515-1531","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Correlating genotype with phenotype using CFTR\u2010mediated whole\u2010cell Cl<sup>\u2212<\/sup> currents in human nasal epithelial cells"],"prefix":"10.1113","volume":"600","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1803-6434","authenticated-orcid":false,"given":"Sabrina","family":"Noel","sequence":"first","affiliation":[{"name":"INSERM U1151 Institut Necker\u2010Enfants Malades  Paris France"},{"name":"Universit\u00e9 de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6925-6256","authenticated-orcid":false,"given":"Nathalie","family":"Servel","sequence":"additional","affiliation":[{"name":"INSERM U1151 Institut Necker\u2010Enfants Malades  Paris France"},{"name":"Universit\u00e9 de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8985-9625","authenticated-orcid":false,"given":"Aur\u00e9lie","family":"Hatton","sequence":"additional","affiliation":[{"name":"INSERM U1151 Institut Necker\u2010Enfants Malades  Paris France"},{"name":"Universit\u00e9 de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5039-3568","authenticated-orcid":false,"given":"Anita","family":"Golec","sequence":"additional","affiliation":[{"name":"INSERM U1151 Institut Necker\u2010Enfants Malades  Paris France"},{"name":"Universit\u00e9 de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2062-8682","authenticated-orcid":false,"given":"Mayuree","family":"Rodrat","sequence":"additional","affiliation":[{"name":"School of Physiology Pharmacology and Neuroscience University of Bristol  Bristol UK"},{"name":"Center of Research and Development for Biomedical Instrumentation Institute of Molecular Biosciences Mahidol University  Nakhon Pathom Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0348-2004","authenticated-orcid":false,"given":"Demi R. 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