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| Status |
Public on Dec 01, 2016 |
| Title |
Renal Fanconi syndrome and hypoposphatemic rickets in mice deficient for retroviral receptor XPR1 in the nephron |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Tight control of both extracellular and intracellular inorganic phosphate (Pi) levels is critical to the normal functioning of virtually all biochemical and physiological processes. The kidney participates in Pi homeostasis by controlling Pi reabsorption from the primary urine. 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. The molecular identity of transporter(s) involved in the basolateral Pi efflux remains unknown. Recent evidence has suggested that the retroviral receptor XPR1 might be a candidate for this role. Here we show that conditional inactivation of Xpr1 in the renal tubule in mice results in impaired renal Pi reabsorption associated with a generalized proximal tubular dysfunction, or Fanconi syndrome, characterized by glycosuria, aminoaciduria, calciuria and albuminuria. Bone histomorphometry showed that the Xpr1-deficient mice develop hypophosphatemic osteomalacia secondary to the renal dysfunction. The analysis of Pi transport in primary culture of the proximal tubular cells revealed that the Pi efflux was significantly affected in cells devoid of Xpr1. These results identify XPR1 as a major player in Pi homeostasis and as a potential therapeutic target in bone and kidney disorders.
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| Overall design |
Mice with doxycycline (DOX)-inducible, Pax8-rtTA-driven conditional deletion of Xpr1 in the renal tubule (Xpr1lox/lox/Pax8-rtTA/LC1 mice) were treated with DOX for two weeks (2 mg/ml in drinking water). Littermate Xpr1lox/lox mice were used as Controls.
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| Contributor(s) |
Ansermet C, Centeno G, Moor MB, Pradervand S, Auberson M, Nikolaeva S, Gautschi I, Bonny O, Firsov D |
| Citation(s) |
27799484 |
| |
| Submission date |
Sep 28, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Sylvain Pradervand |
| E-mail(s) |
Sylvain.Pradervand@unil.ch
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| Phone |
+41 21 692 39 08
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| Organization name |
UNI Lausanne
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| Department |
CIG
|
| Lab |
DNA Array Facility
|
| Street address |
Genopode
|
| City |
Lausanne |
| ZIP/Postal code |
1015 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA344786 |
| SRA |
SRP090574 |
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