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

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.