Expression of Aquaporin-3 and Aquaporin-4 in Aquaporin-1 Knockout Mice

Kim, Wan Young; Kim, Young Hee; Park, Eun Young; Hwang, Jin Sun; Kim, Yu Mi; Kim, Jin

Abstract

Recent studies demonstrated impaired urinary concentrating ability in AQP1 knockout mice. To establish of the lack of AQP1 was associated with compensatory changes in other aquaporins, we examined the expression of AQP3 and AQP4 in AQP1 knockout mice. In AQP1 (+/+) mice, there was strong basolateral AQP3 immunostaining in principal cells throughout the collecting duct and strong basolateral AQP4 immunostaining in IMCD cells and principal cells in the medulla. In AQP1 (-/-) mice, there was an increase in AQP3 immunostaining in principal cells in cortex and outer medulla, but no changes in cellular distribution of labeling. In contrast, AQP4 immunostaining was slightly decreased and there was a surprising decrease in cell height and disappearance of immunolabeling of the lateral cell membrane in IMCD cells with only basal labeling remaining. Immunnoblot analysis confirmed the increase in AQP3 expression in cortex (259+/-50%, P<.0.01), outer medulla (607+/-115%, P<0.01) and inner medulla (1,289+/-174%, P<0.0001), and the decrease in AQP4 expression in the inner medulla (31+/-2%, P<0.02) of AQP1 (-/-) compared with AQP1 (+/+) mice (values in AQP1 (-/-) expressed as percentage of AQP1 (+/+)). In summary, AQP1 gene deletion is associated with an upregulation of AQP3 and a downregulation of AQP4. Taken together, these observations suggest that AQP3 and AQP4 are differently regulated and the basolateral water channel expression is upregulated in the cortical and outer medullary collecting duct in AQP1 knockout mice. The significance of the disappererance of AQP4 immunoreactivity in the lateral plasma membrane of IMCD cells in AQP1 knockout mice remains to be established.