{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:50:20Z","timestamp":1791978620367,"version":"4.4.0"},"reference-count":10,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2017,4]]},"abstract":"\n Tight control of extracellular and intracellular inorganic phosphate (Pi) levels is critical to most biochemical and physiologic processes. Urinary Pi is freely filtered at the kidney glomerulus and is reabsorbed in the renal tubule by the action of the apical sodium-dependent phosphate transporters, NaPi-IIa\/NaPi-IIc\/Pit2. However, the molecular identity of the protein(s) participating in the basolateral Pi efflux remains unknown. Evidence has suggested that xenotropic and polytropic retroviral receptor 1 (XPR1) might be involved in this process. Here, we show that conditional inactivation of\n Xpr1<\/jats:italic>\n in the renal tubule in mice resulted in impaired renal Pi reabsorption. Analysis of Pi transport in primary cultures of proximal tubular cells or in freshly isolated renal tubules revealed that this\n Xpr1<\/jats:italic>\n deficiency significantly affected Pi efflux. Further, mice with conditional inactivation of\n Xpr1<\/jats:italic>\n in the renal tubule exhibited generalized proximal tubular dysfunction indicative of Fanconi syndrome, characterized by glycosuria, aminoaciduria, calciuria, and albuminuria. Dramatic alterations in the renal transcriptome, including a significant reduction in NaPi-IIa\/NaPi-IIc expression, accompanied these functional changes. Additionally,\n Xpr1<\/jats:italic>\n -deficient mice developed hypophosphatemic rickets secondary to renal dysfunction. These results identify XPR1 as a major regulator of Pi homeostasis and as a potential therapeutic target in bone and kidney disorders.\n <\/jats:p>","DOI":"10.1681\/asn.2016070726","type":"journal-article","created":{"date-parts":[[2016,10,31]],"date-time":"2016-10-31T21:41:06Z","timestamp":1477950066000},"page":"1073-1078","source":"Crossref","is-referenced-by-count":84,"title":["Renal Fanconi Syndrome and Hypophosphatemic Rickets in the Absence of Xenotropic and Polytropic Retroviral Receptor in the Nephron"],"prefix":"10.1681","volume":"28","author":[{"given":"Camille","family":"Ansermet","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias B.","family":"Moor","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Centeno","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muriel","family":"Auberson","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothy Zhang","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Baron","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Nikolaeva","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology and"},{"name":"Institute of Evolutionary Physiology and Biochemistry, St. Petersburg, Russia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Haenzi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalya","family":"Katanaeva","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Gautschi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Katanaev","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology and"},{"name":"School of Biomedicine, Far Eastern Federal University, Vladivostok, Russia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Rotman","sequence":"additional","affiliation":[{"name":"Services of Pathology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Koesters","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Pierre et Marie Curie, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Schild","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvain","family":"Pradervand","sequence":"additional","affiliation":[{"name":"Genomic Technologies Facility, University of Lausanne, Lausanne, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Bonny","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology and"},{"name":"Nephrology, Department of Medicine, University Hospital of Lausanne, Lausanne, Switzerland; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitri","family":"Firsov","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2016,10,31]]},"reference":[{"key":"B1-20230829","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1105\/tpc.000745","article-title":"Identification and characterization of the Arabidopsis PHO1 gene involved in phosphate loading to the xylem.","volume":"14","author":"Hamburger","year":"2002","journal-title":"Plant Cell"},{"key":"B2-20230829","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1111\/j.1365-313X.2011.04532.x","article-title":"Over-expression of PHO1 in Arabidopsis leaves reveals its role in mediating phosphate efflux.","volume":"66","author":"Stefanovic","year":"2011","journal-title":"Plant J"},{"key":"B3-20230829","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1016\/j.celrep.2013.05.035","article-title":"Inorganic phosphate export by the retrovirus receptor XPR1 in metazoans.","volume":"3","author":"Giovannini","year":"2013","journal-title":"Cell Reports"},{"key":"B4-20230829","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.febslet.2013.12.013","article-title":"Expression of the mammalian Xenotropic Polytropic Virus Receptor 1 (XPR1) in tobacco leaves leads to phosphate export.","volume":"588","author":"Wege","year":"2014","journal-title":"FEBS Lett"},{"key":"B5-20230829","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1038\/ng.3289","article-title":"Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export.","volume":"47","author":"Legati","year":"2015","journal-title":"Nat Genet"},{"key":"B6-20230829","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1038\/nm.1865","article-title":"An efficient and versatile system for acute and chronic modulation of renal tubular function in transgenic mice.","volume":"14","author":"Traykova-Brauch","year":"2008","journal-title":"Nat Med"},{"key":"B7-20230829","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/0167-4889(83)90087-3","article-title":"Energetics of sodium transport in the kidney. Saturation transfer 31P-NMR.","volume":"762","author":"Freeman","year":"1983","journal-title":"Biochim Biophys Acta"},{"key":"B8-20230829","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1007\/s00223-010-9373-0","article-title":"Phenotype presentation of hypophosphatemic rickets in adults.","volume":"87","author":"Beck-Nielsen","year":"2010","journal-title":"Calcif Tissue Int"},{"key":"B9-20230829","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1086\/499410","article-title":"Hereditary hypophosphatemic rickets with hypercalciuria is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3.","volume":"78","author":"Lorenz-Depiereux","year":"2006","journal-title":"Am J Hum Genet"},{"key":"B10-20230829","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1086\/499409","article-title":"SLC34A3 mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria predict a key role for the sodium-phosphate cotransporter NaPi-IIc in maintaining phosphate homeostasis.","volume":"78","author":"Bergwitz","year":"2006","journal-title":"Am J Hum Genet"}],"container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/00001751-201704000-00012","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T19:28:22Z","timestamp":1786130902000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/00001751-201704000-00012"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10,31]]},"references-count":10,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2017]]}},"URL":"https:\/\/doi.org\/10.1681\/asn.2016070726","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.726911554.793537193","asserted-by":"object"}]},"ISSN":["1046-6673","1533-3450"],"issn-type":[{"value":"1046-6673","type":"print"},{"value":"1533-3450","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10,31]]}}}