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Renal Fanconi Syndrome and Hypophosphatemic Rickets in the Absence of Xenotropic
and Polytropic Retroviral Receptor in the Nephron
#MMPMID27799484
Ansermet C
; Moor MB
; Centeno G
; Auberson M
; Hu DZ
; Baron R
; Nikolaeva S
; Haenzi B
; Katanaeva N
; Gautschi I
; Katanaev V
; Rotman S
; Koesters R
; Schild L
; Pradervand S
; Bonny O
; Firsov D
J Am Soc Nephrol
2017[Apr]; 28
(4
): 1073-1078
PMID27799484
show ga
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 Xpr1 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 Xpr1 deficiency significantly affected Pi
efflux. Further, mice with conditional inactivation of Xpr1 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, 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.
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