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Npt2a and Npt2c in mice play distinct and synergistic roles in inorganic phosphate metabolism and skeletal development.

Authors: Segawa, H  Onitsuka, A  Furutani, J  Kaneko, I  Aranami, F  Matsumoto, N  Tomoe, Y  Kuwahata, M  Ito, M  Matsumoto, M  Li, M  Amizuka, N  Miyamoto, K 
Citation: Segawa H, etal., Am J Physiol Renal Physiol. 2009 Sep;297(3):F671-8. doi: 10.1152/ajprenal.00156.2009. Epub 2009 Jul 1.
Pubmed: (View Article at PubMed) PMID:19570882
DOI: Full-text: DOI:10.1152/ajprenal.00156.2009

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare autosomal recessively inherited disorder, characterized by hypophosphatemia, short stature, rickets and/or osteomalacia, and secondary absorptive hypercalciuria. HHRH is caused by a defect in the sodium-dependent phosphate transporter (NaPi-IIc/Npt2c/NPT2c), which was thought to have only a minor role in renal phosphate (P(i)) reabsorption in adult mice. In fact, mice that are null for Npt2c (Npt2c(-/-)) show no evidence for renal phosphate wasting when maintained on a diet with a normal phosphate content. To obtain insights and the relative importance of Npt2a and Npt2c, we now studied Npt2a(-/-)Npt2c(+/+), Npt2a(+/-)Npt2c(-/-), and Npt2a(-/-)Npt2c(-/-) double-knockout (DKO). DKO mice exhibited severe hypophosphatemia, hypercalciuria, and rickets. These findings are different from those in Npt2a KO mice that show only a mild phosphate and bone phenotype that improve over time and from the findings in Npt2c KO mice that show no apparent abnormality in the regulation of phosphate homeostasis. Because of the nonredundant roles of Npt2a and Npt2c, DKO animals showed a more pronounced reduction in P(i) transport activity in the brush-border membrane of renal tubular cells than that in the mice with the single-gene ablations. A high-P(i) diet after weaning rescued plasma phosphate levels and the bone phenotype in DKO mice. Our findings thus showed in mice that Npt2a and Npt2c have independent roles in the regulation of plasma P(i) and bone mineralization.


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CRRD Object Information
CRRD ID: 7242924
Created: 2013-04-26
Species: All species
Last Modified: 2013-04-26
Status: ACTIVE


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