{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T07:18:17Z","timestamp":1791011897694,"version":"4.1.0"},"reference-count":17,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2010,11]]},"abstract":"\n Klotho is a membrane protein participating in the inhibitory effect of FGF23 on the formation of 1,25-dihydroxyvitamin-D\n 3<\/jats:sub>\n [1,25(OH)\n 2<\/jats:sub>\n D\n 3<\/jats:sub>\n ]. It participates in the regulation of renal tubular phosphate reabsorption and stimulates renal tubular Ca\n 2+<\/jats:sup>\n reabsorption. Klotho hypomorphic mice ( klotho\n hm<\/jats:sup>\n ) suffer from severe growth deficit, rapid aging, and early death, events largely reversed by a vitamin D-deficient diet. The present study explored the role of Klotho deficiency in mineral and electrolyte metabolism. To this end, klotho\n hm<\/jats:sup>\n mice and wild-type mice ( klotho\n +\/+<\/jats:sup>\n ) were subjected to a normal (D\n +<\/jats:sup>\n ) or vitamin D-deficient (D\n \u2212<\/jats:sup>\n ) diet or to a vitamin D-deficient diet for 4 wk and then to a normal diet (D\n \u2212\/+<\/jats:sup>\n ). At the age of 8 wk, body weight was significantly lower in klotho\n hm<\/jats:sup>\n D\n +<\/jats:sup>\n mice than in klotho\n +\/+<\/jats:sup>\n D\n +<\/jats:sup>\n mice, klotho\n hm<\/jats:sup>\n D\n \u2212<\/jats:sup>\n mice, and klotho\n hm<\/jats:sup>\n D\n \u2212\/+<\/jats:sup>\n mice. Plasma concentrations of 1,25(OH)\n 2<\/jats:sub>\n D\n 3,<\/jats:sub>\n adrenocorticotropic hormone (ACTH), antidiuretic hormone (ADH), and aldosterone were significantly higher in klotho\n hm<\/jats:sup>\n D\n +<\/jats:sup>\n mice than in klotho\n +\/+<\/jats:sup>\n D\n +<\/jats:sup>\n mice. Plasma volume was significantly smaller in klotho\n hm<\/jats:sup>\n D\n \u2212\/+<\/jats:sup>\n mice, and plasma urea, Ca\n 2+<\/jats:sup>\n , phosphate and Na\n +<\/jats:sup>\n , but not K\n +<\/jats:sup>\n concentrations were significantly higher in klotho\n hm<\/jats:sup>\n D\n +<\/jats:sup>\n mice than in klotho\n +\/+<\/jats:sup>\n D\n +<\/jats:sup>\n mice. The differences were partially abrogated by a vitamin D-deficient diet. Moreover, the hyperaldosteronism was partially reversed by Ca\n 2+<\/jats:sup>\n -deficient diet. Ussing chamber experiments revealed a marked increase in amiloride-sensitive current across the colonic epithelium, pointing to enhanced epithelial sodium channel (ENaC) activity. A salt-deficient diet tended to decrease and a salt-rich diet significantly increased the life span of klotho\n hm<\/jats:sup>\n D\n +<\/jats:sup>\n mice. In conclusion, the present observation disclose that the excessive formation of 1,25(OH)\n 2<\/jats:sub>\n D\n 3<\/jats:sub>\n in Klotho-deficient mice results in extracellular volume depletion, which significantly contributes to the shortening of life span.\n <\/jats:p>","DOI":"10.1152\/ajprenal.00233.2010","type":"journal-article","created":{"date-parts":[[2010,8,18]],"date-time":"2010-08-18T22:00:12Z","timestamp":1282168812000},"page":"F1171-F1177","source":"Crossref","is-referenced-by-count":58,"title":["Hyperaldosteronism in Klotho-deficient mice"],"prefix":"10.1152","volume":"299","author":[{"given":"Stephanie S.","family":"Fischer","sequence":"first","affiliation":[{"name":"Department of Physiology, University of T\u00fcbingen, T\u00fcbingen;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela S.","family":"Kempe","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of T\u00fcbingen, T\u00fcbingen;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina B.","family":"Leibrock","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of T\u00fcbingen, T\u00fcbingen;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rexhep","family":"Rexhepaj","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of T\u00fcbingen, T\u00fcbingen;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balasaheb","family":"Siraskar","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of T\u00fcbingen, T\u00fcbingen;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna M.","family":"Boini","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of T\u00fcbingen, T\u00fcbingen;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa F.","family":"Ackermann","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of T\u00fcbingen, T\u00fcbingen;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"F\u00f6ller","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of T\u00fcbingen, T\u00fcbingen;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berthold","family":"Hocher","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research\/Institute of Pharmacology, Charit\u00e9, Berlin, Institute of Nutritional Science, University of Potsdam, Germany, and F. Hoffman-La Roche, Limited, pRED-Pharma Research and Early Developement, Basel, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin P.","family":"Rosenblatt","sequence":"additional","affiliation":[{"name":"Centers for Proteomics and Systems Biology, The Brown Foundation Institute of Molecular Medicine, SRB, Houston; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Kuro-o","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Lang","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of T\u00fcbingen, T\u00fcbingen;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2000.00965.x"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/0010-4825(91)90033-6"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2004.03.090"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1126\/science.1135901"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-009-0636-4"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1097\/01.mnh.0000232885.81142.83"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/36285"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1126\/science.1112766"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1515\/CCLM.2006.046"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05-5432fje"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00248.2006"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000124224.48962.32"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1097\/MNH.0b013e3281c55f02"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1210\/me.2003-0048"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000025781.16723.68"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.0101.2001"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1210\/endo.143.2.8657"}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajprenal.00233.2010","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T20:17:37Z","timestamp":1567973857000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajprenal.00233.2010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,11]]},"references-count":17,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2010,11]]}},"alternative-id":["10.1152\/ajprenal.00233.2010"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.00233.2010","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.4943959.4876060","asserted-by":"object"}]},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,11]]}}}