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

## TL;DR

A lack of SLC26A9 function in newborn mice leads to mucus buildup and severe breathing problems, highlighting its role in lung health.

## Contribution

This study reveals the critical role of SLC26A9 in neonatal respiratory function and mucociliary clearance.

## Key findings

- Genetic deletion of Slc26a9 causes severe neonatal respiratory distress and high mortality.
- SLC26A9 deficiency leads to MUC5B-positive mucus plugs and reduced chloride secretion in airways.
- Neonatal Slc26a9–/– mice show hypoxic epithelial degeneration and sterile neutrophilic inflammation.

## Abstract

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.

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