{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T06:18:52Z","timestamp":1789193932031,"version":"build-2803163510"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,8,1]],"date-time":"2016-08-01T00:00:00Z","timestamp":1470009600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB699\/A4"],"award-info":[{"award-number":["SFB699\/A4"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>\n                      The basolateral chloride channel ClC\u2010Kb facilitates Cl reabsorption in the distal nephron of the human kidney. Functional mutations in\n                      <jats:styled-content style=\"fixed-case\">CLCNKB<\/jats:styled-content>\n                      are associated with Bartter's syndrome type 3, a hereditary salt\u2010losing nephropathy. To address the function of ClC\u2010K2\n                      <jats:italic>in\u00a0vivo<\/jats:italic>\n                      , we generated ClC\u2010K2\u2010deficient mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      ClC\u2010K2\u2010deficient mice were generated using\n                      <jats:styled-content style=\"fixed-case\">TALEN<\/jats:styled-content>\n                      technology.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      ClC\u2010K2\u2010deficient mice were viable and born in a Mendelian ratio. ClC\u2010K2\u2212\/\u2212 mice showed no gross anatomical abnormalities, but they were growth retarded. The 24\u2010h urine volume was increased in ClC\u2010K2\u2212\/\u2212 mice (4.4\u00a0\u00b1\u00a00.6 compared with 0.9\u00a0\u00b1\u00a00.2\u00a0mL per 24\u00a0h in wild\u2010type littermates;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.001). Accordingly, ambient urine osmolarity was markedly reduced (590\u00a0\u00b1\u00a039 vs. 2216\u00a0\u00b1\u00a0132\u00a0mosmol\u00a0L\n                      <jats:sup>\u22121<\/jats:sup>\n                      in wild types;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001). During water restriction (24\u00a0h), urinary osmolarity increased to 1633\u00a0\u00b1\u00a0153 and 3769\u00a0\u00b1\u00a0129\u00a0mosmol\u00a0L\n                      <jats:sup>\u22121<\/jats:sup>\n                      in ClC\u2010K2\u2212\/\u2212 and wild\u2010type mice (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a012;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001), accompanied by a loss of body weight of 12\u00a0\u00b1\u00a00.4 and 8\u00a0\u00b1\u00a00.2% respectively (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001). ClC\u2010K2\u2212\/\u2212 mice showed an increased renal sodium excretion and compromised salt conservation during a salt\u2010restricted diet. The salt\u2010losing phenotype of ClC\u2010K2\u2212\/\u2212 mice was associated with a reduced plasma volume, hypotension, a slightly reduced glomerular filtration rate, an increased renal prostaglandin E2 generation and a massively stimulated renin\u2013angiotensin system. Clckb\u2212\/\u2212 mice showed a reduced sensitivity to furosemide and were completely resistant to thiazides.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Loss of ClC\u2010K2 compromises\n                      <jats:styled-content style=\"fixed-case\">TAL<\/jats:styled-content>\n                      function and abolishes salt reabsorption in the distal convoluted tubule. Our data suggest that ClC\u2010K2 is crucial for renal salt reabsorption and concentrating ability. ClC\u2010K2\u2010deficient mice in most aspects mimic patients with Bartter's syndrome type 3.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apha.12755","type":"journal-article","created":{"date-parts":[[2016,7,16]],"date-time":"2016-07-16T03:33:59Z","timestamp":1468640039000},"page":"198-211","source":"Crossref","is-referenced-by-count":49,"title":["Salt\u2010losing nephropathy in mice with a null mutation of the Clcnk2 gene"],"prefix":"10.1111","volume":"218","author":[{"given":"A.","family":"Grill","sequence":"first","affiliation":[{"name":"Institute of Physiology University of Regensburg Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I. 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