Expression of Na<SUP>+</SUP>/Phosphate Cotransporter in Hypophosphatemic Mouse Kidney
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The hypophosphatemic (Hyp) mouse is a useful model for studying certain genetic defects in renal phosphate (P<SUB>i</SUB>) handling in humans. Sodium-dependent phosphate transport activity was measured in brush border membrane vesicle (BBMV) prepared from renal cortex and in <I>Xenopus</I> oocytes that had been injected with renal poly (A) <I>+</I>RNA. Pi transport activity in Hyp mice was significantly reduced compared with the control. Northern blot analysis revealed that the level of NaP<SUB>i</SUB>-7 mRNA was reduced in Hyp mice. Hybrid depletion study showed that the decrease in P<SUB>i</SUB>transport activity in Hyp mice was primarily due to reduced expression of NaP<SUB>i</SUB>-7 mRNA. Immunohistochemical staining for control mice confirmed the localization of NaP<SUB>i</SUB>-7 protein in the brush border membrane (BBM) of proximal convoluted tubules. In contrast, the staining was decreased in the membrane, but increased in intracellular structures of Hyp mice, suggesting that an abnormality of endocytosis/exocytosis in BBM is also involved in Hyp mutation. In conclusion, the defect in renal phosphate reabsorption in Hyp mice resulted from a reduction in mRNA and protein for NaP<SUB>i</SUB>-7 in the proximal convoluted tubules of midcortical and superficial nephrons.
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