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Am J Physiol Renal Physiol (July 5, 2005). doi:10.1152/ajprenal.00133.2005
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Submitted on March 31, 2005
Accepted on June 30, 2005

Defective water and glycerol transport in the proximal tubules of AQP7 knockout mice

Eisei Sohara1, Tatemitsu Rai1, Jun-ichi Miyazaki2, A. S. Verkman3, Sei Sasaki1, and Shinichi Uchida1*

1 Department of Nephrology, Tokyo Medical and Dental University, Bunkyo, Tokyo, Japan
2 Division of Stem Cell Regulation Research, Osaka University, Suita, Osaka, Japan
3 Department of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, CA, USA

* To whom correspondence should be addressed. E-mail: suchida.kid{at}tmd.ac.jp.

Aquaporin7 (AQP7) water channel is known as a member of the aquaglyceroporins, which facilitate the transport of glycerol as well as water. Although AQP7 is abundantly expressed on the apical membrane of the proximal straight tubules in the kidney, the physiological role of AQP7 is still unknown. To investigate this, we generated AQP7 knockout mice. The water permeability of the proximal tubule brush border membrane measured by the stopped flow method was slightly but significantly reduced in the AQP7 knockout mice compared with that of wild-type mice (AQP7, 18.0 ± 0.4x10-3 cm/s vs. wild-type, 20.0 ± 0.3x10-3 cm/s). Although AQP7 solo knockout mice did not exhibit a urinary concentrating defect, AQP1/AQP7 double knockout mice had a reduction in urinary concentrating ability compared with AQP1 solo knockout mice, suggesting that the amount of water reabsorbed through AQP7 in the proximal straight tubules is physiologically substantial. On the other hand, AQP7 knockout mice showed marked glyceroluria (AQP7, 1.7 ± 0.34 mg/ml vs. wild-type, 0.005 ± 0.002 mg/ml). This identified a novel glycerol reabsorption pathway in the proximal straight tubules. In two mouse models of proximal straight tubule injury, the cisplatin-induced acute renal failure (ARF) model and the ischemic ARF model, an increase of urine glycerol was observed (pre-treatment, 0.007 ± 0.005 mg/ml; cisplatin, 0.063 ± 0.043 mg/ml; ischemia, 0.076 ± 0.02 mg/ml), suggesting that urine glycerol could be used as a new biomarker for detecting proximal straight tubule injury.




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