Renal-specific and inducible depletion of NaPi-IIc/Slc34A3, the cotransporter mutated in HHRH, does not affect phosphate or calcium homeostasis in mice.

Renal-specific and inducible depletion of NaPi-IIc/Slc34A3, the cotransporter mutated in HHRH, does not affect phosphate or calcium homeostasis in mice. Am J Physiol Renal Physiol. 2014 Feb 19; Authors: Myakala K, Motta S, Murer H, Wagner CA, Koesters R, Biber J, Hernando N Abstract The proximal renal epithelia express three different Na-dependent inorganic phosphate (Pi)-cotransporters: NaPi-IIa/SLC34A1, NaPi-IIc/SLC34A3 and PiT2/SLC20A2. Constitutive mouse knockout models of NaPi-IIa and NaPi-IIc suggested that NaPi-IIa mediates the bulk of renal reabsorption of Pi whereas the contribution of NaPi-IIc to this process is minor and probably restricted to young mice. However, many reports indicate that mutations of NaPi-IIc in humans lead to Hereditary Hypophosphatemic Rickets with Hypercalciuria (HHRH). Here we report the generation of a kidney-specific and inducible NaPi-IIc deficient mouse model based on the loxP: Cre system. We found that the specific removal of the cotransporter from the kidneys of young mice does not impair the capacity of the renal epithelia to transport Pi. Moreover, the levels of Pi in plasma and urine as well as the circulating levels of PTH, FGF-23 and vitamin D3 remained unchanged. These findings are in agreement with the data obtained with the constitutive knockout model and suggest that, under steady-state conditions of normal dietary Pi, NaPi-IIc is not an essential Na/Pi-cotransporter in murine kidneys. However,...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research