Temporal deletion of Aqp11 in mice is linked to the severity of cyst-like disease.

Abstract

Aquaporin 11 (AQP11) is a channel protein with unknown biological function that is expressed in multiple tissues, including the kidney proximal tubule (PT) epithelium. Constitutive deletion of Aqp11 in mice (Aqp11-/-) results in early postnatal vacuolization in the PT and development of apparent cysts at 2 wk of age. Electron microscopy of adult Aqp11-/- mouse PT cells revealed a dilated rough endoplasmic reticulum. These changes may cause renal failure and premature death. This study examined 1) whether postnatal deletion of Aqp11 affects PT injury and cyst formation, 2) the temporal role of Aqp11 deletion on cyst development, and 3) the nature of apparent cysts. Tamoxifen-inducible Aqp11-/- mice were generated (Ti-Aqp11-/-). Deletion of Aqp11 at postnatal days (P) P2, P4, P6, P8, and P12 was investigated. Deranged renal development, especially in kidney cortex, PT cell vacuolization, and apparent tubular cysts developed only in mice where Aqp11 gene disruption was induced until P8. Aqp11 gene deletion from P12 onward did not result in a clear deficiency in renal development, PT injury, or cyst formation. Intraperitoneal injection of biotinylated-dextran (10 kDa) into adult mice resulted in extensive endocytic dextran uptake in both cystic Aqp11-/- and control PT epithelium, respectively. This suggests that apparent cysts are not membrane-enclosed structures but represent PT dilations. We conclude that Aqp11-/- mice develop cyst-like dilated proximal tubules without documented cysts at time of death.