{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T01:19:51Z","timestamp":1783559991427,"version":"3.55.0"},"reference-count":48,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2008,10,14]],"date-time":"2008-10-14T00:00:00Z","timestamp":1223942400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK35124"],"award-info":[{"award-number":["DK35124"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL59198"],"award-info":[{"award-number":["HL59198"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY13574"],"award-info":[{"award-number":["EY13574"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EB00415"],"award-info":[{"award-number":["EB00415"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK72517"],"award-info":[{"award-number":["DK72517"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL73856"],"award-info":[{"award-number":["HL73856"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK66194"],"award-info":[{"award-number":["DK66194"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["0365027Y"],"award-info":[{"award-number":["0365027Y"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2009,2]]},"abstract":"<jats:p>\n                    Mutations in aquaporin\u20102 (AQP2) that interfere with its cellular processing can produce autosomal recessive nephrogenic diabetes insipidus (NDI). Prior gene knock\u2010in of the human NDI\u2010causing AQP2 mutation T126M produced mutant mice that died by age 7 days. Here, we used a novel \u201cconditional gene knock\u2010in\u201d strategy to generate adult, AQP2\u2010T126M mutant mice. Mice separately heterozygous for floxed wild\u2010type AQP2 and AQP2\u2010T126M were bred to produce hemizygous mice, which following excision of the wild\u2010type AQP2 gene by tamoxifen\u2010induced Cre\u2010recombinase gave AQP2\n                    <jats:sup>T126M\/\u2010<\/jats:sup>\n                    mice. AQP2\n                    <jats:sup>T126M\/_<\/jats:sup>\n                    mice were polyuric (9\u201014 ml urine\/ day) compared to AQP2\n                    <jats:sup>+\/+<\/jats:sup>\n                    mice (1.6 ml\/day) and had reduced urine osmolality (400\n                    <jats:italic>vs.<\/jats:italic>\n                    1800 mosmol). Kidneys of AQP2\n                    <jats:sup>T126M\/\u2010<\/jats:sup>\n                    mice expressed core\u2010glycosylated AQP2\u2010T126M protein in an endoplasmic reticulum pattern. Screening of candidate protein folding \u201ccorrectors\u201d in AQP2\u2010T126M\u2010transfected kidney cells showed increased AQP2\u2010T126M plasma membrane expression with the Hsp90 inhibitor 17\u2010allylamino\u201017\u2010demethoxygeldanamycin (17\u2010AAG). 17\u2010AAG increased urine osmolality in AQP2\n                    <jats:sup>T126M\/\u2010<\/jats:sup>\n                    mice by &gt;300 mosmol but had no effect in AQP2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. Kidneys of 17\u2010AAG\u2010treated AQP2\n                    <jats:sup>T126M\/\u2010<\/jats:sup>\n                    mice showed partial rescue of defective AQP2\u2010T126M cellular processing. Our results establish an adult mouse model of NDI and demonstrate partial restoration of urinary concentration function by a compound currently in clinical trials for other indications.\u2014Yang, B., Zhao, D., Verkman, A. S. Hsp90 inhibitor partially corrects nephrogenic diabetes insipidus in a conditional knock\u2010in mouse model of aquaporin\u20102 mutation.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    23, 503\u2010512 (2009)\n                  <\/jats:p>","DOI":"10.1096\/fj.08-118422","type":"journal-article","created":{"date-parts":[[2008,10,14]],"date-time":"2008-10-14T23:14:15Z","timestamp":1224026055000},"page":"503-512","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Hsp90 inhibitor partially corrects nephrogenic diabetes insipidus in a conditional knock\u2010in mouse model of aquaporin\u20102 mutation"],"prefix":"10.1096","volume":"23","author":[{"given":"Baoxue","family":"Yang","sequence":"first","affiliation":[{"name":"Departments of Medicine and Physiology, Cardiovascular Research Institute University of California San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Physiology, Cardiovascular Research Institute University of California San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. S.","family":"Verkman","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Physiology, Cardiovascular Research Institute University of California San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,10,14]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00041552-199801000-00007"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00024.2001"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00387.2002"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1042\/BC20040120"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2008.03.004"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8140421"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2006.02.004"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005040371"},{"key":"e_1_2_6_10_1","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1159\/000020686","article-title":"Defective processing and trafficking of water channels in nephrogenic diabetes insipidus","volume":"8","author":"Kamsteeg E. 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