Urine electrolyte, mineral, and protein excretion in NHERF-2 and NHERF-1 null mice

textabstractThe adaptor proteins sodium/hydrogen exchanger regulatory factor (NHERF)-1 and NHERF-2 have overlapping tissue distribution in renal cells and overlapping specificity in their binding to renal transporters and other proteins. To compare the kidney-specific differences in the function of these adaptor proteins, NHERF-1 and NHERF-2 null mice were compared with wild-typecontrol mice. In NHERF-2 null mice, the renal proximal tubuleabundance and distribution of NHERF-1 and NHERF-3 were not different from those in wild-typeanimals. The glomerular expression of podocalyxinand ZO-1 also did not differ. NHERF-1 null mice had increased urinary excretion of phosphate, calcium, and uric acid compared with wild-typecontrol and NHERF-2 null mice. Because of the association between NHERF-2 and podocalyxinin glomeruli and ClC-5 in the renal proximal tubule, the urinary excretion of protein was determined. There were no differences in the urinary excretion of protein or low-molecular-weight proteins between wild-typecontrol, NHERF-1-/-, and NHERF-2-/-mice. These studies indicate that the increased urinary excretion of phosphate and uric acid are specific to NHERF-1 null mice and highlight the fact that predictions about the role of adaptor proteins such as the NHERF proteins obtained from studies of model cell systems must be confirmed in whole animals.