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  • 1
    ISSN: 1432-2013
    Keywords: Key wordsGy mouse ; Inorganic phosphate ; Sodium-gradient-dependent phosphate transport ; Brush border membrane ; Kidney
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The X-linked Gy mutation is closely linked, but not allelic, to Hyp and is characterized by rickets, hypophosphatemia, decreased renal tubular maximum for phosphate (Pi) reabsorption (TmP) and a specific reduction in renal brush-border membrane (BBM) Na+-Pi cotransport. Gy mice, like their normal littermates, respond to a low-Pi diet with an increase in BBM Na+-Pi cotransport, but fail to show an adaptive increase in Tmp. Using an antibody raised against the NH2 terminal peptide of the rat renal-specific Na+-Pi cotransporter (NaPi-2) and a NaPi-2 cDNA probe, we examined the effect of the Gy mutation and low-Pi diet (0.03% Pi) on NaPi-2 protein and mRNA abundance. The reduction in BBM Na+-Pi cotransport in Gy mice (51 ± 5% of normal, P 〈 0.05) was associated with a decrease in NaPi-2 protein (46 ± 12% of normal, P 〈 0.05) and mRNA abundance (76 ± 5%, P 〈 0.05). The low-Pi diet elicited a two- to three-fold increase in Na+-Pi cotransport in both normal and Gy mice that was accompanied by a large increase in NaPi-2 protein (10.2-fold in normal and 16.9-fold in Gy mice) and a modest increase in NaPi-2 mRNA (1.3-fold in both mouse strains, P 〈 0.05). The present data demonstrate that (1) the renal defect in BBM Pi transport in Gy mice can be ascribed to a deficit in NaPi-2 protein and mRNA abundance, (2) both normal and Gy mice respond to low Pi with an adaptive increase in NaPi-2 protein that exceeds the increase in Na+-Pi cotransport activity and NaPi-2 mRNA, (3) the adaptive increase in NaPi-2 protein and mRNA are not sufficient for the overall increase in TmP following Pi restriction.
    Type of Medium: Electronic Resource
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