Identification and functional analysis of regulatory factors for fibroblast growth factor 23/klotho/inorganic sensor system

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In the present study, we investigated inorganic phosphate (Pi) metabolism in the type IIa and type IIc sodium-dependent Pi cotransporter gene knockout mice (Npt2a^<-/->Npt2c>^<-/-> DKO mice). To clarify the relative importance of Npt2a and Npt2c, we studied DKO mice These mice exhibited severe hypophosphatemia, hypercalciuria, and rickets. This phenotype is similar to that seen inhereditary hypophosphatemic rickts with hypercalciuria (HHRH) which is characterized by hypophosphate, short stature, rickets, and/or osteomalacia, with secondary absorptive hypercalciuria. Studies of the DKO animals showed that the expansion of the late hypertrophic zone in the bone, which is a characteristic feature of rickets, might be secondary to the impaired apoptosis of these cells. In the analysis of DNA microarray in the kidney of DKO mice, we identified the clone encode calcium activated chloride channel 6 (CLCA6) and analyzed its function in Xenopus oocytes and renal epithelial cells. The present study indicates that CLCA6 modulates the activity of type III renal sodium-dependent Pi cotransporter PiT2 in DKO mice.