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Molecular and Cellular Biology, September 2005, p. 7770-7779, Vol. 25, No. 17
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.17.7770-7779.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Disruption of Aquaporin-11 Produces Polycystic Kidneys following Vacuolization of the Proximal Tubule

Yoshiyuki Morishita,1 Toshiyuki Matsuzaki,2 Mariko Hara-chikuma,3 Ayaka Andoo,4 Mariko Shimono,4 Asako Matsuki,5 Katsuki Kobayashi,7 Masahiro Ikeda,4 Tadashi Yamamoto,5 Alan Verkman,3 Eiji Kusano,1 Shigeo Ookawara,1 Kuniaki Takata,2 Sei Sasaki,6 and Kenichi Ishibashi1,6,7*

Department of Nephrology and Anatomy, Jichi Medical School, Tochigi 329-0498, Japan,1 Department of Anatomy and Cell Biology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan,2 Cardiovascular Research Institute, UCSF, San Francisco, California 94143-0521,3 Department of Veterinary Pharmacology, University of Miyazaki, Miyazaki 889-2192, Japan,4 Institute of Nephrology, Niigata University Graduate School of Medical and Dental Science, Niigata 951-8510, Japan,5 Department of Nephrology, Tokyo Medical and Dental University, Tokyo 113-8591, Japan,6 Clinical Research Center, Chiba-East National Hospital, Chiba 260-8712, Japan7

Received 18 March 2005/ Returned for modification 6 May 2005/ Accepted 9 June 2005

Aquaporin-11 (AQP11) has been identified with unusual pore-forming NPA (asparagine-proline-alanine) boxes, but its function is unknown. We investigated its potential contribution to the kidney. Immunohistochemistry revealed that AQP11 was localized intracellularly in the proximal tubule. When AQP11 was transfected in CHO-K1 cells, it was localized in intracellular organelles. AQP11-null mice were generated; these mice exhibited vacuolization and cyst formation of the proximal tubule. AQP11-null mice were born normally but died before weaning due to advanced renal failure with polycystic kidneys, in which cysts occupied the whole cortex. Remarkably, cyst epithelia contained vacuoles. These vacuoles were present in the proximal tubules of newborn mice. In 3-week-old mice, these tubules contained multiple cysts. Primary cultured cells of the proximal tubule revealed an endosomal acidification defect in AQP11-null mice. These data demonstrate that AQP11 is essential for the proximal tubular function. AQP11-null mice are a novel model for polycystic kidney diseases and will provide a new mechanism for cystogenesis.


* Corresponding author. Mailing address: Department of Molecular Biology Research, Institute of Clinical Investigation, Chiba-East National Hospital, National Hospital Organization, 673 Nitona, Chuou-ku, Chiba 260-8712, Japan. Phone: 81-43-261-5171. Fax: 81-43-268-2613. E-mail: kishiba{at}nitona.hosp.go.jp.


Molecular and Cellular Biology, September 2005, p. 7770-7779, Vol. 25, No. 17
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.17.7770-7779.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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