{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T06:04:22Z","timestamp":1779516262986,"version":"3.53.1"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["493665037"],"award-info":[{"award-number":["493665037"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["457011590(AR1092\/2\u20102)"],"award-info":[{"award-number":["457011590(AR1092\/2\u20102)"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      The epithelial sodium channel ENaC consists of the subunits \u03b1, \u03b2, and \u03b3 and is activated at an individual channel level by proteolytic processing. Murine \u03b3ENaC contains a distal polybasic tract 186\n                      <jats:sup>RKRK<\/jats:sup>\n                      mediating proteolytic ENaC activation by serine proteases in\u00a0vitro. The relevance of ENaC activation at this cleavage site for sodium homeostasis in\u00a0vivo is unknown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Mice were generated carrying a mutation of the distal polybasic tract (RKRK186QQQQ or \u03b3ENaC\n                      <jats:sup>ki\/ki<\/jats:sup>\n                      ) using CRISP\/Cas9. Sodium homeostasis and proteolytic processing of \u03b3ENaC were investigated under a low sodium diet, pharmacological ENaC blockade, and induction of nephrotic syndrome.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Under control conditions, the response to bolus amiloride was reduced in \u03b3ENaC\n                      <jats:sup>ki\/ki<\/jats:sup>\n                      mice compared to \u03b3ENaC\n                      <jats:sup>wt\/wt<\/jats:sup>\n                      mice. Under a low sodium diet for 4\u2009days, urinary sodium excretion was similarly lowered in both genotypes; however, \u03b3ENaC\n                      <jats:sup>ki\/ki<\/jats:sup>\n                      mice required significantly higher plasma aldosterone concentrations. Both genotypes were similarly tolerant to amiloride exposure for 4\u2009days and developed similar sodium retention and body weight gain after induction of nephrotic syndrome. Proteolytic processing of \u03b3ENaC leading to increased expression of distally cleaved \u03b3ENaC at ~54\u2009kDa was stimulated in both \u03b3ENaC\n                      <jats:sup>wt\/wt<\/jats:sup>\n                      and \u03b3ENaC\n                      <jats:sup>ki\/ki<\/jats:sup>\n                      mice under all interventions without an appreciable difference in the migration pattern.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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 \u03b3ENaC in these mice appears to be compensated for by the involvement of other adjacent cleavage sites.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apha.70228","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T07:41:18Z","timestamp":1777275678000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hyperaldosteronism in Mice Lacking the Distal Polybasic Tract of the \u03b3\u2010Subunit of the Epithelial Sodium Channel During Sodium Restriction"],"prefix":"10.1111","volume":"242","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1473-377X","authenticated-orcid":false,"given":"Daniel","family":"Essigke","sequence":"first","affiliation":[{"name":"Internal Medicine IV, Department of Diabetology, Endocrinology and Nephrology University Hospital T\u00fcbingen  T\u00fcbingen Germany"},{"name":"Institute for Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Munich at the University of T\u00fcbingen  T\u00fcbingen Germany"},{"name":"German Center for Diabetes Research (DZD)  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Zaher","family":"Kalo","sequence":"additional","affiliation":[{"name":"Internal Medicine IV, Department of Diabetology, Endocrinology and Nephrology University Hospital T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"W\u00f6rn","sequence":"additional","affiliation":[{"name":"Internal Medicine IV, Department of Diabetology, Endocrinology and Nephrology University Hospital T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8625-8114","authenticated-orcid":false,"given":"Xia\u2010Qing","family":"Li","sequence":"additional","affiliation":[{"name":"Internal Medicine IV, Department of Diabetology, Endocrinology and Nephrology University Hospital T\u00fcbingen  T\u00fcbingen Germany"},{"name":"Department of Nephrology Peking University Shenzhen Hospital  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0169-3948","authenticated-orcid":false,"given":"Bernhard N.","family":"Bohnert","sequence":"additional","affiliation":[{"name":"Internal Medicine IV, Department of Diabetology, Endocrinology and Nephrology University Hospital T\u00fcbingen  T\u00fcbingen Germany"},{"name":"Institute for Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Munich at the University of T\u00fcbingen  T\u00fcbingen Germany"},{"name":"German Center for Diabetes Research (DZD)  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8849-4794","authenticated-orcid":false,"given":"Anja","family":"Schork","sequence":"additional","affiliation":[{"name":"Internal Medicine IV, Department of Diabetology, Endocrinology and Nephrology University Hospital T\u00fcbingen  T\u00fcbingen Germany"},{"name":"Institute for Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Munich at the University of T\u00fcbingen  T\u00fcbingen Germany"},{"name":"German Center for Diabetes Research (DZD)  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1407-9023","authenticated-orcid":false,"given":"Andreas L.","family":"Birkenfeld","sequence":"additional","affiliation":[{"name":"Internal Medicine IV, Department of Diabetology, Endocrinology and Nephrology University Hospital T\u00fcbingen  T\u00fcbingen Germany"},{"name":"Institute for Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Munich at the University of T\u00fcbingen  T\u00fcbingen Germany"},{"name":"German Center for Diabetes Research (DZD)  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Ott","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Biological Cybernetics  T\u00fcbingen 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