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Bartter syndrome is a hypokalemic, salt\u2010losing tubulopathy caused by impaired TAL function. Pathogenic variants in\n SLC12A1<\/jats:italic>\n or\n KCNJ1<\/jats:italic>\n cause antenatal Bartter syndrome, and variants in\n CLCNKB<\/jats:italic>\n result in classical Bartter syndrome. Although all variants impair TAL electrolyte transport, their effects on mineral handling differ. In contrast to antenatal forms, classical Bartter syndrome is frequently associated with hypomagnesemia, a feature also found in Gitelman syndrome resulting from pathogenic variants in\n SLC12A3<\/jats:italic>\n , expressed in the distal convoluted tubule (DCT). The mechanisms underlying these distinct clinical phenotypes are not understood.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Clcnkb\u2010<\/jats:italic>\n and\n Slc12a3<\/jats:italic>\n \u2010deficient mice as well as human kidneys were investigated. The abundance and localization of electrolyte and mineral transporters and stereological parameters were assessed by immunohistochemistry. Gene and protein expression was determined in\n Clcnkb<\/jats:italic>\n \u2010deficient mice.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In human kidney, both ClC\u2010K channels and their essential subunit Barttin were found in TAL, DCT, and collecting system.\n Clcnkb<\/jats:italic>\n \u2010deficient mice showed complete ablation of\n Clcnkb<\/jats:italic>\n and reduced DCT and connecting tubule volumes. Furthermore, DCT magnesium channels and select basolateral magnesium transporters were markedly reduced in\n Clcnkb<\/jats:italic>\n \u2010deficient mice, similar to\n Slc12a3<\/jats:italic>\n \u2010deficient mice. In contrast, the overall abundance of calcium transport proteins was largely preserved.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n ClC\u2010K channels are expressed in the TAL and DCT in mouse and human kidneys.\n Clcnkb<\/jats:italic>\n ablation reduces TRPM magnesium channel expression and DCT tubule volume, providing a likely explanation for the frequently observed hypomagnesemia in classical Bartter syndrome.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/apha.70295","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T10:43:07Z","timestamp":1787308987000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Reduced Expression of Magnesium Transport Proteins in the Distal Convoluted Tubule of\n Clcnkb<\/i>\n \u2010Deficient Mice May Explain Urinary Magnesium Wasting in Classical Bartter Syndrome"],"prefix":"10.1111","volume":"242","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9962-8276","authenticated-orcid":false,"given":"Marleen L. 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