{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T05:56:13Z","timestamp":1788328573833,"version":"build-2803163510"},"reference-count":32,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2001,1,1]]},"abstract":"<jats:p>The CLC-K1 chloride channel is a kidney-specific CLC chloride channel expressed in the thin ascending limb of Henle's loop (tAL). Recently, we determined that Clcnk1\u2212\/\u2212 mice show nephrogenic diabetes insipidus (NDI). To investigate the pathogenesis of impaired urinary concentrating ability, we analyzed renal functions of Clcnk1\u2212\/\u2212 mice in more detail. The osmolar clearance-to-creatinine clearance ratio was not significantly different between Clcnk1+\/\u2212 and Clcnk1+\/+ mice. Fractional excretion of sodium, chloride, and urea was also not significantly affected in Clcnk1\u2212\/\u2212 mice. These results indicate that the polyuria observed in Clcnk1\u2212\/\u2212 mice was water diuresis and not osmotic diuresis. The papillary osmolarity in Clcnk1\u2212\/\u2212 mice was significantly lower than that in Clcnk1+\/+ mice under a hydrated condition, and it did not increase even after water deprivation. Sodium and chloride contents in the inner medulla in Clcnk1\u2212\/\u2212 mice were at about one-half the levels observed in Clcnk1+\/+ mice. Furthermore, the accumulation of urea was also impaired in Clcnk1\u2212\/\u2212 mice, suggesting that the overall countercurrent system was impaired by a defect of its single component, chloride transport in the tAL. The aldose reductase mRNA abundance in Clcnk1\u2212\/\u2212 mice was decreased, further evincing that inner medullary tonicity is decreased in Clcnk1\u2212\/\u2212 mice. We concluded that NDI in Clcnk1\u2212\/\u2212 mice resulted from an impairment in the generation of inner medullary hypertonicity by a dysfunction of the countercurrent systems.<\/jats:p>","DOI":"10.1152\/ajprenal.2001.280.1.f79","type":"journal-article","created":{"date-parts":[[2017,12,23]],"date-time":"2017-12-23T13:34:15Z","timestamp":1514036055000},"page":"F79-F87","source":"Crossref","is-referenced-by-count":62,"title":["Impaired solute accumulation in inner medulla of<i>Clcnk1<\/i>\u2212\/\u2212 mice kidney"],"prefix":"10.1152","volume":"280","author":[{"given":"Norikazu","family":"Akizuki","sequence":"first","affiliation":[{"name":"Second Department of Internal Medicine, Tokyo Medical and Dental University, Tokyo 113-8519, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichi","family":"Uchida","sequence":"additional","affiliation":[{"name":"Second Department of Internal Medicine, Tokyo Medical and Dental University, Tokyo 113-8519, 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