<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Role of the epithelial Cl- channel SLC26A9 in the murine airway epithelium"^^ . "The alternative chloride channel SLC26A9, member of the SoLute Carrier 26 family, has been genetically involved in the pathogenesis of airway mucus obstruction in CF, allergic disease and diffuse non-CF bronchiectasis, supporting a potential role of SLC26A9 as a modifier in muco-obstructive lung diseases. Furthermore, in vivo experiments in a mouse model of Th2-driven airway disease revealed that SLC26A9-mediated chloride secretion is critical to prevent airway mucus obstruction, supporting the potential contribution of SLC26A9 to airway surface hydration in the airway epithelium. These findings support SLC26A9 as a promising therapeutic target in CF to potentially bypass the impaired CFTR-mediated chloride secretion. Nevertheless, the in vivo role of SLC26A9 under physiological conditions remains unclear. Hence, in this work, the function of SLC26A9 was investigated in a developmental manner (newborn, juvenile and adult stage) by characterizing the pulmonary phenotype of Slc26a9-/- mice. Furthermore, we evaluated how the genetic deletion of Slc26a9 changes the mortality rate of βENaC-Tg mice, which is a mouse model of CF-like lung disease.\r\nNewborn Slc26a9-/- mice displayed severe acute respiratory distress due to muco-inflammatory phenotype leading to significant mortality. The mucus plugging of the newborn Slc26a9-/- mice was extended throughout the whole respiratory tree. The experiments also demonstrated that airway mucus plugging limits ventilation in newborn Slc26a9-/- mice and trigger neutrophil-mediated inflammation probably via epithelial hypoxic necrosis releasing IL-1α. Interestingly, this muco-obstructive phenotype was not observed at the juvenile and adult stage. However, neutrophilic inflammation persists up to adulthood in the lungs of surviving Slc26a9-/- mice, but trends to decrease over time, suggesting that surviving Slc26a9-/- mice resolve the initial muco-inflammatory phenotype. By monitoring the double mutant βENaC-Tg/Slc26a9-/- mice and littermate controls, it was determined that the deletion of Slc26a9 increases the mortality of βENaC-Tg mice.\r\nIn summary, the data demonstrate for the first time that SLC26A9-mediated Cl-/fluid secretion is particularly relevant for lung health at birth. These findings suggest a critical role of SLC26A9 to maintain airway surface hydration and mucus clearance at the air-breathing adaptation period. The longitudinal characterization of the Slc26a9-/- mice revealed an age-dependent resolution of the initial muco-inflammatory phenotype. However, the implications of this airway disease resolution process on the pathogenesis of muco-obstructive lung diseases, including CF is not yet clear. Furthermore, the modification of survival in βENaC-Tg/Slc26a9-/- mice, implicates that Slc26a9 might impact the lung phenotype in a pathophysiological context. Finally, unravelling the understanding of SLC26A9 function in the pathogenesis of muco-obstructive lung diseases may lead to improve non-CFTR directed therapies for patients with CF."^^ . "2021" . . . . . . . "Pamela"^^ . "Millar Büchner"^^ . "Pamela Millar Büchner"^^ . . . . . . "Role of the epithelial Cl- channel SLC26A9 in the murine airway epithelium (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Role of the epithelial Cl- channel SLC26A9 in the murine airway epithelium (PDF)"^^ . . . "Thesis_final version_Pamela Millar-Buchner_.pdf"^^ . . . "Role of the epithelial Cl- channel SLC26A9 in the murine airway epithelium (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Role of the epithelial Cl- channel SLC26A9 in the murine airway epithelium (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Role of the epithelial Cl- channel SLC26A9 in the murine airway epithelium (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Role of the epithelial Cl- channel SLC26A9 in the murine airway epithelium (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #29972 \n\nRole of the epithelial Cl- channel SLC26A9 in the murine airway epithelium\n\n" . "text/html" . .