X-linked hypophosphatamic vitamin D-resistant rickets is characterized by decreased renal proximal tubular reabsorption of phosphate. This disorder is related to abnormal expression of sodium-phosphate transporter (NA+/Pi) in the epithelia of the renal tubules. The Hyp mouse is an animal model of this disorder. Northern blot analysis and in-situ hybridization showed that mRNA for NA+/Pi transporter was decreased in the Hyp mouse. Western blot and immunohistochemistry showed that the protein level for NA+/Pi transporter was decreed as compared to genetically matched control mice. The transcriptional rate of this gene was also decreased in the Hyp mouse. Dietary Pi restriction resulted in an adaptive increase in Na+/Pi transport activities, mRNA levels and protein levels in both adult Hyp and control mice. The goal of this proposal is to study the ontogeny of Na+/Pi transporter expression in control and Hyp mice and to characterize the regulation of gene expression by dietary Pi restriction. The project is aimed (l) to characterize the ontogenic changes in expression of renal Na+/Pi transporter in control and mice at mRNA, protein and functional activity levels; (2) to determine the molecular mechanisms the ontogeny of renal Na+/Pi transporter expression in control and Hyp mice by studying the transcriptional rate of gene, mRNA stability and protein turnover; and (3) to characterize the regulation of expression of the renal Na+/Pi transporter by low Pi diet during early life in control and Hyp mice.
