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Am J Physiol Renal Physiol 294: F1001-F1007, 2008. First published February 6, 2008; doi:10.1152/ajprenal.00504.2007
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Urine electrolyte, mineral, and protein excretion in NHERF-2 and NHERF-1 null mice

Rochelle Cunningham,1 Ali Esmaili,2 Eric Brown,1 Rajat S. Biswas,1 Rakhilya Murtazina,3 Mark Donowitz,3 Henry B. Dijkman,4 Johan van der Vlag,4 Boris M. Hogema,5 Hugo R. De Jonge,5 Shirish Shenolikar,6 James B. Wade,1 and Edward J. Weinman1,7

1University of Maryland School of Medicine, 2Union Memorial Hospital, and 3Johns Hopkins University School of Medicine, Baltimore, Maryland; 4Radboud University Nijmegen Medical Centre, Nijmegen and 5Erasmus University Medical Center, Rotterdam, The Netherlands; 6Duke University Medical Center, Durham, North Carolina; and 7Department of Veterans Affairs Medical Center, Baltimore, Maryland

Submitted 29 October 2007 ; accepted in final form 2 February 2008

ABSTRACT

The 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-type control mice. In NHERF-2 null mice, the renal proximal tubule abundance and distribution of NHERF-1 and NHERF-3 were not different from those in wild-type animals. The glomerular expression of podocalyxin and ZO-1 also did not differ. NHERF-1 null mice had increased urinary excretion of phosphate, calcium, and uric acid compared with wild-type control and NHERF-2 null mice. Because of the association between NHERF-2 and podocalyxin in 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-type control, 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.

mouse kidney; PDZ proteins; sodium/hydrogen exchanger regulatory factor


Address for reprint requests and other correspondence: R. Cunningham, Univ. of Maryland School of Medicine, 22 S. Greene St., N3W143, Baltimore, MD 21201 (e-mail: rcunning{at}medicine.umaryland.edu)






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