{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T21:17:45Z","timestamp":1778275065564,"version":"3.51.4"},"reference-count":47,"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":[[2006,7]]},"abstract":"<jats:p>To investigate the underlying causes for aldose reductase deficiency-induced diabetes insipidus, we carried out studies with three genotypic groups of mice. These included wild-type mice, knockout mice, and a newly created bitransgenic line that was homozygous for both the aldose reductase null mutation and an aldose reductase knockin transgene driven by the kidney-specific cadherin promoter to direct transgene expression in the collecting tubule epithelial cells. We found that from early renal developmental stages onward, urine osmolality did not exceed 1,000 mosmol\/kgH<jats:sub>2<\/jats:sub>O in aldose reductase-deficient mice. The functional defects were correlated with significant renal cellular and structural abnormalities that included cell shrinkage, apoptosis, disorganized tubular and vascular structures, and segmental atrophy. In contrast, the transgenic aldose reductase expression in the bitransgenic mice largely but incompletely rescued urine concentrating capacity and significantly improved renal cell survival, cellular morphology, and renal structures. Together, these results suggest that aldose reductase not only plays important roles in osmoregulation and medullary cell survival but may also be essential for the full maturation of the urine concentrating mechanism.<\/jats:p>","DOI":"10.1152\/ajprenal.00506.2005","type":"journal-article","created":{"date-parts":[[2006,2,1]],"date-time":"2006-02-01T03:43:31Z","timestamp":1138765411000},"page":"F186-F195","source":"Crossref","is-referenced-by-count":22,"title":["Genetic restoration of aldose reductase to the collecting tubules restores maturation of the urine concentrating mechanism"],"prefix":"10.1152","volume":"291","author":[{"given":"James Y.","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W. Y.","family":"Tam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sidney","family":"Tam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaochun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guohua","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenny F. L.","family":"Chau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janet D.","family":"Klein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sookja K.","family":"Chung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeff M.","family":"Sands","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen S. M.","family":"Chung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.3648"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1988.254.6.C788"},{"key":"R3","doi-asserted-by":"crossref","unstructured":"Bonjour JPand Malvin RL.Stimulation of ADH release by the renin-angiotensin system.Am J Physiol218: 1555\u20131559, 1970.","DOI":"10.1152\/ajplegacy.1970.218.6.1555"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1988.46"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1996.247"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.19.11429"},{"key":"R7","doi-asserted-by":"crossref","unstructured":"Chung Sand LaMendola J.Cloning and sequence determination of human placental aldose reductase gene.J Biol Chem264: 14775\u201314777, 1989.","DOI":"10.1016\/S0021-9258(18)63766-4"},{"key":"R8","unstructured":"Cooke CRand Steenburg RW.Effects of aldosterone and cortisol on the renal concentrating mechanism.J Lab Clin Med82: 784\u2013792, 1973."},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2004.06.053"},{"key":"R10","unstructured":"Esther CR Jr, Howard TE, Marino EM, Goddard JM, Capecchi MR and Bernstein KE.Mice lacking angiotensin-converting enzyme have low blood pressure, renal pathology, and reduced male fertility.Lab Invest74: 953\u2013965, 1996."},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1991.71.4.1081"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000113244.37857.AC"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1172\/JCI104305"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1995.tb20408.x"},{"key":"R15","doi-asserted-by":"crossref","unstructured":"Han KH, Woo SK, Kim WY, Park SH, Cha JH, Kim J, and Kwon HM.Maturation of TonEBP expression in developing rat kidney.Am J Physiol Renal Physiol287: F878\u2013F885, 2004.","DOI":"10.1152\/ajprenal.00047.2004"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.16.5840-5846.2000"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1999.277.4.F599"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20031838"},{"key":"R19","doi-asserted-by":"crossref","unstructured":"Jung JY, Kim YH, Cha JH, Han KH, Kim MK, Madsen KM, and Kim J.Expression of aldose reductase in developing rat kidney.Am J Physiol Renal Physiol283: F481\u2013F491, 2002.","DOI":"10.1152\/ajprenal.00332.2001"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.2.630"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00326.2001"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1997.272.1.F3"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.2376"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00272.2004"},{"key":"R25","unstructured":"Lal S, Szwergold BS, Taylor AH, Randall WC, Kappler F, and Brown TR.Production of fructose and fructose-3-phosphate in maturing rat lenses.Invest Ophthalmol Vis Sci36: 969\u2013973, 1995."},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M407224200"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00240.2003"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308703100"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1172\/JCI104084"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.278.2.H339"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1998.274.4.F753"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.52.030190.003553"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000045050.19544.B2"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M004678200"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.8.12.2095"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00331.2001"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-198505000-00013"},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1989.256.4.F563"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115991"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000016443.50138.CD"},{"key":"R41","unstructured":"Sheikh-Hamad D, Nadkarni V, Choi YJ, Truong LD, Wideman C, Hodjati R, and Gabbay KH.Cyclosporine A inhibits the adaptive responses to hypertonicity: a potential mechanism of nephrotoxicity.J Am Soc Nephrol12: 2732\u20132741, 2001."},{"key":"R42","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1992.262.3.C776"},{"key":"R43","doi-asserted-by":"publisher","DOI":"10.1016\/S1044-7431(03)00096-4"},{"key":"R44","doi-asserted-by":"publisher","DOI":"10.1016\/S1043-6618(05)80087-8"},{"key":"R45","doi-asserted-by":"publisher","DOI":"10.1152\/advan.00034.2004"},{"key":"R46","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.16.5753-5760.2002"},{"key":"R47","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1990.258.1.C156"}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajprenal.00506.2005","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T11:03:22Z","timestamp":1627038202000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajprenal.00506.2005"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,7]]},"references-count":47,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2006,7]]}},"alternative-id":["10.1152\/ajprenal.00506.2005"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.00506.2005","relation":{},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,7]]}}}