title: Renal Fanconi Syndrome and Hypophosphatemic Rickets in the Absence of Xenotropic and Polytropic Retroviral Receptor in the Nephron.
abstract: 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 ofXpr1in 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 thisXpr1deficiency significantly affected Pi efflux. Further, mice with conditional inactivation ofXpr1in 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,Xpr1-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.
authors: Department of Pharmacology and Toxicology and.
authors: Camille
authors: C
authors: Ansermet
authors: Department of Pharmacology and Toxicology and.
authors: Matthias B
authors: MB
authors: Moor
authors: Department of Pharmacology and Toxicology and.
authors: Gabriel
authors: G
authors: Centeno
authors: Department of Pharmacology and Toxicology and.
authors: Muriel
authors: M
authors: Auberson
authors: Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts.
authors: Dorothy Zhang
authors: DZ
authors: Hu
authors: Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts.
authors: Roland
authors: R
authors: Baron
authors: Department of Pharmacology and Toxicology and.|Institute of Evolutionary Physiology and Biochemistry, St. Petersburg, Russia.
authors: Svetlana
authors: S
authors: Nikolaeva
authors: Department of Pharmacology and Toxicology and.
authors: Barbara
authors: B
authors: Haenzi
authors: Department of Pharmacology and Toxicology and.
authors: Natalya
authors: N
authors: Katanaeva
authors: Department of Pharmacology and Toxicology and.
authors: Ivan
authors: I
authors: Gautschi
authors: Department of Pharmacology and Toxicology and.|School of Biomedicine, Far Eastern Federal University, Vladivostok, Russia.
authors: Vladimir
authors: V
authors: Katanaev
authors: Services of Pathology and.
authors: Samuel
authors: S
authors: Rotman
authors: Université Pierre et Marie Curie, Paris, France.
authors: Robert
authors: R
authors: Koesters
authors: Department of Pharmacology and Toxicology and.
authors: Laurent
authors: L
authors: Schild
authors: Genomic Technologies Facility, University of Lausanne, Lausanne, Switzerland.
authors: Sylvain
authors: S
authors: Pradervand
authors: Department of Pharmacology and Toxicology and dmitri.firsov@unil.ch olivier.bonny@unil.ch.|Nephrology, Department of Medicine, University Hospital of Lausanne, Lausanne, Switzerland; and.
authors: Olivier
authors: O
authors: Bonny
authors: Department of Pharmacology and Toxicology and dmitri.firsov@unil.ch olivier.bonny@unil.ch.
authors: Dmitri
authors: D
authors: Firsov
mesh_terms: D000818:Animals; D005198:Fanconi Syndrome / Q000209:etiology*; D005260:Female; D008297:Male; D051379:Mice; D009399:Nephrons; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D011991:Receptors, Virus / Q000502:physiology*; D063730:Rickets, Hypophosphatemic / Q000209:etiology*; D000089842:Xenotropic and Polytropic Retrovirus Receptor
chemical_list: D043562:Receptors, G-Protein-Coupled; D011991:Receptors, Virus; D000089842:Xenotropic and Polytropic Retrovirus Receptor; C000715268:Xpr1 protein, mouse
keywords: Fanconi syndrome; hypophosphatemic rickets; kidney; phosphate homeostasis; retroviral receptor XPR1