{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:26:35Z","timestamp":1753878395970,"version":"3.41.2"},"reference-count":43,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>The aim of this study was to determine whether water or solute transport plays a critical role in AQP3\u2010mediated urine concentrating ability, using AQP3 knockout (AQP3\u2010KO) mice and a novel mouse model in which the AQP3 gene coding region is replaced with AQP4 cDNA (AQP4\u2010KI).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>AQP3\u2010KO and AQP4\u2010KI mice were characterized using Western blot and immunofluorescence to confirm the absence of AQP3 and the in\u00a0situ replacement of AQP4. Urinary output, osmolality and urea concentration were measured in mouse models under various conditions, including water deprivation, acute urea loading and high protein intake.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>AQP3\u2010KO mice exhibited a significantly increased daily urine output (6 times that in wild\u2010type mice) and reduced urinary osmolality (&lt;\u20091000\u2009mOsm\/kg), with a marked inability to concentrate urea and osmolality in response to water deprivation, urea loading or high protein intake. In contrast, AQP4\u2010KI mice showed restoration of urine output, urinary osmolality and urea concentration, approaching wild\u2010type levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In situ replacement of AQP3 with AQP4 restores AQP3\u2010mediated water permeability in the renal collecting duct, rescuing the nephrogenic diabetes insipidus (NDI) phenotype in AQP3\u2010deficient mice. This study provides evidence that AQP3\u2010mediated water permeability plays a crucial role in the renal urine concentrating mechanism.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.70072","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T10:35:51Z","timestamp":1749638151000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Aquaporin\u20104\u2010Mediated Water Permeability Rescues Aquaporin\u20103 Deficiency Caused Nephrogenic Diabetes Insipidus"],"prefix":"10.1111","volume":"241","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1434-1458","authenticated-orcid":false,"given":"Yi","family":"Ying","sequence":"first","affiliation":[{"name":"State Key Laboratory of Vascular Homeostasis and Remodeling, Department of Pharmacology, School of Basic Medical Sciences Peking University  Beijing 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