Urine electrolyte, mineral, and protein excretion in NHERF-2 and NHERF-1 null mice.
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.
Cunningham
Rochelle
R
Univ. of Maryland School of Medicine, 22 S. Greene St., N3W143, Baltimore, MD 21201, USA. rcunning@medicine.umaryland.edu
Esmaili
Ali
A
Brown
Eric
E
Biswas
Rajat S
RS
Murtazina
Rakhilya
R
Donowitz
Mark
M
Dijkman
Henry B
HB
van der Vlag
Johan
J
Hogema
Boris M
BM
De Jonge
Hugo R
HR
Shenolikar
Shirish
S
Wade
James B
JB
Weinman
Edward J
EJ
D000818:Animals; D004573:Electrolytes / Q000652:urine*; D007672:Kidney Cortex / Q000648:ultrastructure; D007684:Kidney Tubules / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D010750:Phosphoproteins / Q000172:deficiency* / Q000235:genetics; D011507:Proteinuria / Q000235:genetics*; D012016:Reference Values; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics
D004573:Electrolytes; D010750:Phosphoproteins; D017923:Sodium-Hydrogen Exchangers; C093376:sodium-hydrogen exchanger regulatory factor