{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:51:34Z","timestamp":1787500294423,"version":"build-2736575974"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2019,8,22]],"date-time":"2019-08-22T00:00:00Z","timestamp":1566432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100006447","name":"University of Zurich","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006447","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Swiss National Centre for Competence in Research \u2018Kidney"},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["310030_173276\/1"],"award-info":[{"award-number":["310030_173276\/1"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Loss-of-function mutations in the sodium chloride (NaCl) co-transporter (NCC) of the renal distal convoluted tubule (DCT) cause Gitelman syndrome with hypokalemic alkalosis, hypomagnesemia and hypocalciuria. Since Gitelman patients are usually diagnosed around adolescence, we tested the idea that a progressive regression of the DCT explains the late clinical onset of the syndrome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>NCC wild-type and knockout (ko) mice were studied at Days 1, 4 and 10 and 6\u2009weeks after birth using blood plasma analysis and morphological and biochemical methods.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Plasma aldosterone levels and renal renin messenger RNA expression were elevated in NCC ko mice during the first days of life. In contrast, plasma ion levels did not differ between genotypes at age 10\u2009days, but a significant hypomagnesemia was observed in NCC ko mice at 6\u2009weeks. Immunofluorescent detection of parvalbumin (an early DCT marker) revealed that the fractional cortical volume of the early DCT is similar for mice of both genotypes at Day 4, but is significantly lower at Day 10 and is almost zero at 6\u2009weeks in NCC ko mice. The DCT atrophy correlates with a marked reduction in the abundance of the DCT-specific Mg2+ channel TRPM6 (transient receptor potential cation channel subfamily M member 6) and an increased proteolytic activation of the epithelial Na+ channel (ENaC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>After an initial outgrowth, DCT development lags behind in NCC ko mice. The impaired DCT development associates at Day 1 and Day 10 with elevated renal renin and plasma aldosterone levels and activation of ENaC, respectively, suggesting that Gitelman syndrome might be present much earlier in life than is usually expected. Despite an early downregulation of TRPM6, hypomagnesemia is a rather late symptom.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ndt\/gfz172","type":"journal-article","created":{"date-parts":[[2019,7,24]],"date-time":"2019-07-24T15:16:52Z","timestamp":1563981412000},"page":"411-432","source":"Crossref","is-referenced-by-count":18,"title":["Loss of sodium chloride co-transporter impairs the outgrowth of the renal distal convoluted tubule during renal development"],"prefix":"10.1093","volume":"35","author":[{"given":"Christina","family":"Schnoz","sequence":"first","affiliation":[{"name":"Institute of Anatomy, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique","family":"Carrel","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, University of Zurich, Zurich, 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