What question did this study set out to answer?

This research aims to determine the effects of a specific mutation in the γ-subunit of the epithelial sodium channel on sodium homeostasis and hyperaldosteronism during sodium restriction.

April 29, 2026Open Access

Hyperaldosteronism in Mice Lacking the Distal Polybasic Tract of the γ‐Subunit of the Epithelial Sodium Channel During Sodium Restriction

Key Points

This research aims to determine the effects of a specific mutation in the γ-subunit of the epithelial sodium channel on sodium homeostasis and hyperaldosteronism during sodium restriction.
Utilized CRISPR/Cas9 to create a specific mutation in the distal polybasic tract of γENaC.
Investigated sodium homeostasis and proteolytic processing of γENaC under a low sodium diet and pharmacological ENaC blockade.
Assessed the impact of nephrotic syndrome induction on the established models.
Mice with the RKRK186QQQQ mutation developed hyperaldosteronism during sodium restriction.
No noticeable differences were observed in the migration patterns of proteolytic processing across all interventions.
Alternative cleavage sites compensated for the proteolytic processing of γENaC in the mutated mice.

Abstract

AIMS: mediating proteolytic ENaC activation by serine proteases in vitro. The relevance of ENaC activation at this cleavage site for sodium homeostasis in vivo is unknown. METHODS: ) using CRISP/Cas9. Sodium homeostasis and proteolytic processing of γENaC were investigated under a low sodium diet, pharmacological ENaC blockade, and induction of nephrotic syndrome. RESULTS: mice under all interventions without an appreciable difference in the migration pattern. CONCLUSION: Mice harboring the RKRK186QQQQ mutation of the distal polybasic tract develop hyperaldosteronism under a low sodium diet, pointing to the relevance of this tract for sodium preservation. However, proteolytical processing of γENaC in these mice appears to be compensated for by the involvement of other adjacent cleavage sites.

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