Aquaporin-4 is expressed in basolateral membranes of proximal tubule S3 segments in mouse kidney

Because of the availability of knockout mouse models to examine renal trans port mechanisms, it has become increasingly important to describe the cellu lar distribution of major renal transporters in mice. We have used immunocy tochemistry and freeze-fracture electron microscopy to compare the renal di stribution of aquaporin-4 (AQP4) with that previously described in rat. In rat kidney AQP4 is present exclusively in basolateral membranes of collecti ng duct principal cells. In mice, however, AQP4 was also detected by immuno cytochemistry in basolateral membranes of proximal tubule S3 segments, and not detected in S1 and S2 segments of proximal tubule. Freeze-fracture elec tron microscopy revealed orthogonal arrays of intramembrane particles (OAPs ) on the basolateral membranes of the S3 segment. In AQP4-knockout mice, im munostaining was absent and OAPs were found neither in collecting ducts nor in the S3 segment of the proximal tubule. The urinary concentrating capaci ty after deletion of both AQP1 and AQP4 was further reduced compared with t hat of AQP1 or AQP4 null mice, suggesting an additive effect of AQP1 and AQ P4 in the concentrating mechanism. The functional significance of the appar ent species-dependent expression of AQP4 in proximal tubules is unknown, bu t may relate to physiological differences between rats and mice.