{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T21:45:35Z","timestamp":1778276735757,"version":"3.51.4"},"reference-count":24,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2006,6]]},"abstract":"<jats:p> Hypokalemia is a prominent feature of Gitelman syndrome and a common side effect of thiazide use in the treatment of hypertension. It is widely recognized that genetic or pharmacological inhibition of the renal thiazide-sensitive sodium-chloride cotransporter (NCC) initiates the potentially severe renal potassium loss observed in these settings. Surprisingly, hypokalemia has not been detected in NCC (\u2212\/\u2212) mice maintained on normal rodent diets (Schultheis PJ, Lorenz JN, Meneton P, Nieman ML, Riddle TM, Flagella M, Duffy JJ, Doetschman T, Miller ML, and Shull GE. J Biol Chem 273: 29150\u201329155, 1998). We show that modest reduction of dietary potassium induced a marked reduction in plasma potassium and elevated renal potassium excretion in NCC (\u2212\/\u2212) mice that was associated with a pronounced polydipsia and polyuria of central origin. These findings are consistent with the development of potassium depletion in NCC (\u2212\/\u2212) mice and were not seen in wild-type mice maintained on the same low-potassium diet. In addition, plasma aldosterone levels were significantly elevated in NCC (\u2212\/\u2212) mice even in the presence of a low-potassium diet. Collectively, these findings suggest an early central component to the polyuria of Gitelman syndrome and show that both elevated aldosterone and dietary potassium content contribute to the development of hypokalemia in Gitelman syndrome. Therefore, NCC (\u2212\/\u2212) mice are more sensitive to reductions in dietary potassium than wild-type mice and become hypokalemic, thus more faithfully representing the Gitelman phenotype seen in humans. <\/jats:p>","DOI":"10.1152\/ajprenal.00421.2005","type":"journal-article","created":{"date-parts":[[2006,1,25]],"date-time":"2006-01-25T03:08:42Z","timestamp":1138158522000},"page":"F1416-F1420","source":"Crossref","is-referenced-by-count":65,"title":["Hypokalemia in a mouse model of Gitelman's syndrome"],"prefix":"10.1152","volume":"290","author":[{"given":"Ryan G.","family":"Morris","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewout J.","family":"Hoorn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark A.","family":"Knepper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI108813"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00055.2004"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0401704101"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1172\/JCI111598"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2736(84)90114-7"},{"key":"R6","unstructured":"Gitelman HJ, Graham JB, and Welt LG. A new familial disorder characterized by hypokalemia and hypomagnesemia. Trans Assoc Am Physicians 79: 221\u2013235, 1966."},{"key":"R7","doi-asserted-by":"crossref","unstructured":"Hollander W Jr, Winters RW, Willams TF, Bradley J, Oliver J, and Welt LG. Defect in the renal tubular reabsorption of water associated with potassium depletion in rats. Am J Physiol 189: 557\u2013563, 1957.","DOI":"10.1152\/ajplegacy.1957.189.3.557"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.111.6.825"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00111.2003"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1159\/000013303"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198701293160502"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.24.14552"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000138234.18569.63"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1989.256.5.F932"},{"key":"R15","doi-asserted-by":"crossref","unstructured":"Malnic G, Klose RM, and Giebisch G. Micropuncture study of renal potassium excretion in the rat. Am J Physiol 206: 674\u2013686, 1964.","DOI":"10.1152\/ajplegacy.1964.206.4.674"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1172\/JCI104707"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1172\/JCI104084"},{"key":"R18","unstructured":"Mujais SK and Katz AI. Potassium deficiency. In: The Kidney Physiology and Pathophysiology (3rd ed.), edited by Seldin DW and Giebisch G. Philadelphia, PA: Lippincott Williams and Wilkins, 2000, p. 1615\u20131646."},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1990.258.2.F423"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1977.233.6.F544"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1990.258.1.F199"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.44.29150"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1038\/ng0196-24"},{"key":"R24","unstructured":"Whang R and Welt LG. Observations in experimental magnesium depletion. Clin Res 10: 68, 1962."}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajprenal.00421.2005","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T23:13:35Z","timestamp":1567984415000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajprenal.00421.2005"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,6]]},"references-count":24,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2006,6]]}},"alternative-id":["10.1152\/ajprenal.00421.2005"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.00421.2005","relation":{},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,6]]}}}