Submitted on October 29, 2007
Accepted on February 2, 2008
Urine Electrolyte, Mineral, and Protein Excretion in NHERF-2 and NHERF-1 Null Mice
Rochelle Marie Cunningham1*, Ali Esmaili2, Eric Brown1, Rajat S. Biswas3, Rakhilya Murtazina4, Mark Donowitz5, Henry B. Dijkman6, Johan van der Vlag6, Boris M. Hogema7, Hugo R. De Jonge8, Shirish Shenolikar9, James B. Wade10, and Edward J. Weinman11
1 Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States
2 Medicine, Union Memorial Hospital, Baltimore, Maryland, United States
3 Baltimore, Maryland, United States; Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States
4 Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
5 Baltimore, Maryland, United States; Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
6 Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
7 Erasmus University Medical Center, Rotterdam, Netherlands
8 Erasmus University of Rotterdam, Netherlands Antilles
9 Duke University Medical Center, Durham, North Carolina, United States
10 Department of Physiology, University of Maryland, Baltimore, Maryland, United States
11 Medicine, Department of Veterans Affairs Medical Center, Baltimore, Maryland, United States; Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States
* To whom correspondence should be addressed. E-mail: rcunning{at}medicine.umaryland.edu.
The adaptor proteins NHERF-1 and NHERF-2 have overlapping tissue distribution in renal cells and overlapping specificity in their binding to renal transporters and other proteins. In order to compare the kidney specific differences in the function of these adaptor proteins, NHERF-1 and NHERF-2 null mice were compared to wild-type controls. In NHERF-2 null mice, the renal proximal tubule abundance and distribution of NHERF-1 and NHERF-3 was not different than 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 to wild-type controls 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 controls, 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 needs to be confirmed in whole animals.
