{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T03:56:30Z","timestamp":1791950190999,"version":"4.3.4"},"reference-count":51,"publisher":"American Society for Clinical Investigation","issue":"14","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health\/NHLBI","doi-asserted-by":"crossref","award":["T32 HL007752"],"award-info":[{"award-number":["T32 HL007752"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health\/NIDDK","doi-asserted-by":"crossref","award":["R01DK100315"],"award-info":[{"award-number":["R01DK100315"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,7,26]]},"abstract":"<jats:p>\n                    Different nephron tubule segments perform distinct physiological functions, collectively acting as a blood filtration unit. Dysfunction of the proximal tubule segment can lead to Fanconi renotubular syndrome (FRTS), with major symptoms such as excess excretion of water, glucose, and phosphate in the urine. It has been shown that a mutation in\n                    <jats:italic>HNF4A<\/jats:italic>\n                    is associated with FRTS in humans and that\n                    <jats:italic>Hnf4a<\/jats:italic>\n                    is expressed specifically in proximal tubules in adult rat nephrons. However, little is known about the role of\n                    <jats:italic>Hnf4a<\/jats:italic>\n                    in nephrogenesis. Here, we found that\n                    <jats:italic>Hnf4a<\/jats:italic>\n                    is expressed in both presumptive and differentiated proximal tubules in the developing mouse kidney. We show that\n                    <jats:italic>Hnf4a<\/jats:italic>\n                    is required for the formation of differentiated proximal tubules but is dispensable for the formation of presumptive proximal tubules. Furthermore, we show that loss of\n                    <jats:italic>Hnf4a<\/jats:italic>\n                    decreased the expression of proximal tubule\u2013specific genes. Adult\n                    <jats:italic>Hnf4a<\/jats:italic>\n                    mutant mice presented with FRTS-like symptoms, including polyuria, polydipsia, glycosuria, and phosphaturia. Analysis of the adult\n                    <jats:italic>Hnf4a<\/jats:italic>\n                    mutant kidney also showed proximal tubule dysgenesis and nephrocalcinosis. Our results demonstrate the critical role of\n                    <jats:italic>Hnf4a<\/jats:italic>\n                    in proximal tubule development and provide mechanistic insight into the etiology of FRTS.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.97497","type":"journal-article","created":{"date-parts":[[2018,7,25]],"date-time":"2018-07-25T11:01:04Z","timestamp":1532516464000},"source":"Crossref","is-referenced-by-count":82,"title":["Hnf4a deletion in the mouse kidney phenocopies Fanconi renotubular syndrome"],"prefix":"10.1172","volume":"3","author":[{"given":"Sierra S.","family":"Marable","sequence":"first","affiliation":[{"name":"Division of Pediatric Urology and"},{"name":"Division of Developmental Biology, Cincinnati Children\u2019s Hospital Medical Center (CCHMC), Cincinnati, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunah","family":"Chung","sequence":"additional","affiliation":[{"name":"Division of Pediatric Urology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Adam","sequence":"additional","affiliation":[{"name":"Division of Developmental Biology, Cincinnati Children\u2019s Hospital Medical Center (CCHMC), Cincinnati, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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