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1Department of Medicine, 2Department of Physiology, University of Maryland School of Medicine, and 3Medical Service, Department of Veterans Affairs Medical Center, Baltimore; 4Harbor Hospital Center, Brooklyn, Maryland; and 5Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina
Submitted 15 September 2005 ; accepted in final form 23 October 2005
NHERF-1 binds numerous renal protein targets, including the proximal tubule transporters Na+/H+ exchanger 3 (NHE3) and Na+-phosphate cotransporter 2a (Npt2a). Young NHERF-1/ male mice display defective targeting of Npt2a to apical membranes in the renal proximal tubule and manifest hypophosphatemia and increased urinary excretion of phosphate. The present studies describe the changes in the urinary excretion of phosphate, calcium, uric acid, and sodium in male and female wild-type and NHERF-1 null mice over a time period from 12 to 54 wk of age. Young male and female NHERF-1/ mice demonstrated increased urinary excretion of phosphate and urine phosphate/creatinine ratios. There was an age-related decline in the phosphate/creatinine ratio in mutant mice such that there were no differences between wild-type and NHERF-1/ by 24 to 30 wk of age despite the continued presence of hypophosphatemia. Male and female NHERF-1 null mice also demonstrate increased urine calcium/creatinine and uric acid/creatinine ratios compared with wild-type controls. These studies indicate defects in the renal tubule transport of phosphate, calcium, and uric acid in NHERF-1/ male and female mice that could account for the increased deposition of calcium in the papilla of null mice.
bone density and mineralization; hypophosphatemia; electrolyte excretion
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