{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T09:31:30Z","timestamp":1771061490358,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2013,3,11]],"date-time":"2013-03-11T00:00:00Z","timestamp":1362960000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The water channel aquaporin\u20102 (AQP2) is regulated by the hormone vasopressin, and is essential for renal water handling and overall body water balance.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>AQP2 is expressed in the renal connecting tubule (CNT) and collecting duct (CD). The role of AQP2 in the CD is well established.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Here we generate a novel mouse model with gene deletion of AQP2 in the mouse CNT and use this model to examine the role of AQP2 in this segment.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Knockout (KO) mice have defective renal water handling under basal conditions, with higher urine volume and reduced urine osmolality, but are able to decrease urine volume under conditions of high circulating vasopressin.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>KO mice have no obvious compensatory mechanisms in other transporters.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>KO mice develop a urinary\u2010concentrating defect similar to control mice following lithium chloride treatment. However, the defect in KO mice continued to be more severe than in the control mice, suggesting that the CNT does not play a significant role in the pathology of lithium\u2010induced nephrogenic diabetes insipidus.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our studies indicate that the CNT plays a role in regulating body water balance under basal conditions, but not for maximal concentration of the urine during antidiuresis.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><jats:p><jats:bold>Abstract\u2002<\/jats:bold> Body water balance is regulated via the water channel aquaporin\u20102 (AQP2), which is expressed in the renal connecting tubule (CNT) and collecting duct (CD). The relative roles of AQP2 in the CNT and CD are not fully understood. To study the role of AQP2 in the CNT we generated a mouse model with CNT\u2010specific AQP2 deletion (AQP2\u2010CNT\u2010knockout (KO)). Confocal laser scanning microscopy and immunogold electron microscopy demonstrated an absence of AQP2 in the CNT of AQP2\u2010CNT\u2010KO mice. Twenty\u2010four hour urine output was significantly increased (KO: 3.0 \u00b1 0.3 ml (20 g body weight (BW))<jats:sup>\u22121<\/jats:sup>; wild\u2010type (WT): 1.9 \u00b1 0.3 ml (20 g BW)<jats:sup>\u22121<\/jats:sup>) and urine osmolality decreased (KO: 1179 \u00b1 107 mosmol kg<jats:sup>\u22121<\/jats:sup>; WT: 1790 \u00b1 146 mosmol kg<jats:sup>\u22121<\/jats:sup>) in AQP2\u2010CNT\u2010KO mice compared with controls. After 24 h water restriction, urine osmolality was still significantly lower in AQP2\u2010CNT\u2010KO mice (KO: 2087 \u00b1 169 mosmol kg<jats:sup>\u22121<\/jats:sup>; WT: 2678 \u00b1 144 mosmol kg<jats:sup>\u22121<\/jats:sup>). A significant difference in urine osmolality between groups before desmopressin (dDAVP) (KO: 873 \u00b1 129 mosmol kg<jats:sup>\u22121<\/jats:sup>; WT: 1387 \u00b1 163 mosmol kg<jats:sup>\u22121<\/jats:sup>) was not apparent 2 h after injection, with urine osmolality increased significantly in both groups (KO: 2944 \u00b1 41 mosmol kg<jats:sup>\u22121<\/jats:sup>; WT: 3133 \u00b1 66 mosmol kg<jats:sup>\u22121<\/jats:sup>). Cortical kidney fractions from AQP2\u2010CNT\u2010KO mice had significantly reduced AQP2, with no compensatory changes in sodium potassium chloride cotransporter (NKCC2), AQP3 or AQP4. Lithium chloride treatment increased urine volume and decreased osmolality in both WT and AQP2\u2010CNT\u2010KO mice. After 8 days of treatment, the AQP2\u2010CNT\u2010KO mice still had a significantly higher urine volume and lower urine osmolality, suggesting that the CNT does not play a significant role in the pathology of lithium\u2010induced nephrogenic diabetes insipidus. Our studies indicate that the CNT plays a role in regulating body water balance under basal conditions, but not for maximal concentration of the urine during antidiuresis.<\/jats:p>","DOI":"10.1113\/jphysiol.2012.250852","type":"journal-article","created":{"date-parts":[[2013,1,29]],"date-time":"2013-01-29T10:52:25Z","timestamp":1359456745000},"page":"2205-2219","source":"Crossref","is-referenced-by-count":33,"title":["Genetic ablation of aquaporin\u20102 in the mouse connecting tubules results in defective renal water handling"],"prefix":"10.1113","volume":"591","author":[{"given":"Marleen L. A.","family":"Kortenoeven","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nis Borbye","family":"Pedersen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. Lance","family":"Miller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandra","family":"Rojek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert A.","family":"Fenton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,3,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5000388"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-6386(87)80098-7"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00383.2005"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00266.2003"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2009101077"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00234.2002"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2010070734"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2000.279.5.F874"},{"key":"e_1_2_6_10_1","first-page":"57","article-title":"Desensitization to vasopressin action in the rat kidney medulla: studies on isolated nephron segments","volume":"15","author":"Dublineau I","year":"1992","journal-title":"Ren Physiol Biochem"},{"key":"e_1_2_6_11_1","doi-asserted-by":"crossref","first-page":"F663","DOI":"10.1152\/ajprenal.1995.269.5.F663","article-title":"Aquaporin\u20103 water channel localization and regulation in rat kidney","volume":"269","author":"Ecelbarger CA","year":"1995","journal-title":"Am J Physiol Renal Physiol"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00316.2006"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0401704101"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplegacy.1959.196.4.927"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111880200"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1979.46"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1999.276.1.F96"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00037.2002"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2000.279.3.F552"},{"key":"e_1_2_6_20_1","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1152\/ajplegacy.1961.200.6.1139","article-title":"Micropuncture study of net transtubular movement of water and urea in nondiuretic mammalian kidney","volume":"200","author":"Lassiter WE","year":"1961","journal-title":"Am J Physiol"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00217.2002"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2000.278.4.F530"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117863"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2008.569"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00084.2004"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2008.505"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00158.2005"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.4.1013"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E04-04-0337"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0511324103"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2005.00426.x"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00308.2006"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1996.271.2.F414"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2003.08.005"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0773.1973.tb01512.x"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008216200"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00494.2005"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2Fjphysiol.2012.250852","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/jphysiol.2012.250852","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,29]],"date-time":"2023-10-29T00:25:02Z","timestamp":1698539102000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/jphysiol.2012.250852"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,3,11]]},"references-count":36,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2013,4]]}},"alternative-id":["10.1113\/jphysiol.2012.250852"],"URL":"https:\/\/doi.org\/10.1113\/jphysiol.2012.250852","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,3,11]]}}}