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Lack of SLC26A9-mediated chloride secretion causes mucus plugging and severe respiratory distress in neonatal mice

Solute carrier family 26, member 9 (SLC26A9) is an epithelial chloride channel that was identified as a genetic modifier of disease severity of cystic fibrosis (CF) and other chronic muco-obstructive lung diseases. However, data on the in vivo role of SLC26A9 function in lung health and disease rema...

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Main Authors: Millar-Büchner, Pamela (Author) , Salomon, Johanna J. (Author) , Duerr, Julia (Author) , Spahn, Stephan (Author) , Anagnostopoulou, Pinelopi (Author) , Wagner, Willi Linus (Author) , Wielpütz, Mark Oliver (Author) , Gröne, Hermann-Josef (Author) , Balázs, Anita (Author) , Mall, Marcus A. (Author)
Format: Article (Journal)
Language:English
Published: December 8, 2025
In: The journal of clinical investigation
Year: 2025, Volume: 10, Issue: 23, Pages: 1-13
ISSN:1558-8238
DOI:10.1172/jci.insight.196355
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1172/jci.insight.196355
Verlag, kostenfrei, Volltext: https://insight.jci.org/articles/view/196355
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Author Notes:Pamela Millar-Büchner, Johanna J. Salomon, Julia Duerr, Stephan Spahn, Pinelopi Anagnostopoulou, Willi L. Wagner, Mark O. Wielpütz, Hermann-Josef Groene, Anita Balázs, and Marcus A. Mall
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Summary:Solute carrier family 26, member 9 (SLC26A9) is an epithelial chloride channel that was identified as a genetic modifier of disease severity of cystic fibrosis (CF) and other chronic muco-obstructive lung diseases. However, data on the in vivo role of SLC26A9 function in lung health and disease remain limited. Here, we investigated the effect of genetic deletion of Slc26a9 (Slc26a9–/–) on the pulmonary phenotype of neonatal mice. We found that lack of Slc26a9 causes severe neonatal respiratory distress with high mortality. Histology, immunohistochemistry, and micro-computed tomography imaging studies identified airway obstruction with MUC5B-positive mucus plugs in neonatal Slc26a9–/– mice. Bioelectric measurements demonstrated a reduced transepithelial potential difference indicative of reduced chloride secretion across tracheal explants of neonatal Slc26a9–/– compared with WT mice. In addition, neonatal Slc26a9–/– mice displayed hypoxic degeneration of airway epithelial cells associated with sterile neutrophilic airway inflammation. Collectively, our data show that SLC26A9-mediated chloride secretion is critical for proper mucociliary clearance, respiratory function, and survival after birth, and identify a role for SLC26A9 in neonatal adaptation during the transition from fetal to neonatal life.
Item Description:Veröffentlicht: 17. Oktober 2025
Gesehen am 02.03.2026
Physical Description:Online Resource
ISSN:1558-8238
DOI:10.1172/jci.insight.196355

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