Journal Article

DKFZ-2025-02162

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Lack of SLC26A9-mediated chloride secretion causes mucus plugging and severe respiratory distress in neonatal mice.

Millar-Büchner, P. ; Salomon, J. J. ; Duerr, J. ; Spahn, S. ; Anagnostopoulou, P. ; Wagner, W. L. ; Wielpuetz, M. O. ; Gröne, H.-J.DKFZ* ; Balázs, A. ; Mall, M. A.

2025
JCI Insight Ann Arbor, Michigan

Abstract: 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 to wild-type 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 novel role of SLC26A9 in neonatal adaptation during the transition from fetal to neonatal life.

Keyword(s): Development ; Epithelial transport of ions and water ; Inflammation ; Ion channels ; Pulmonology

Note: 2025 Oct 16;10(23):e196355

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Contributing Institute(s):

1. Zelluläre und Molekulare Pathologie (G130)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2025

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Database coverage:
; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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