Disruption of aquaporin-11 produces polycystic kidneys following vacuolization of the proximal tubule.
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.
Morishita
Yoshiyuki
Y
Department of Nephrology and Anatomy, Jichi Medical School, Tochigi, Japan.
Matsuzaki
Toshiyuki
T
Hara-chikuma
Mariko
M
Andoo
Ayaka
A
Shimono
Mariko
M
Matsuki
Asako
A
Kobayashi
Katsuki
K
Ikeda
Masahiro
M
Yamamoto
Tadashi
T
Verkman
Alan
A
Kusano
Eiji
E
Ookawara
Shigeo
S
Takata
Kuniaki
K
Sasaki
Sei
S
Ishibashi
Kenichi
K
D000818:Animals; D020346:Aquaporins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D001835:Body Weight / Q000235:genetics; D002478:Cells, Cultured; D006224:Cricetinae; D011992:Endosomes / Q000378:metabolism; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D009929:Organ Size / Q000235:genetics; D007690:Polycystic Kidney Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D021381:Protein Transport; D014617:Vacuoles / Q000378:metabolism*
C503878:Aqp11 protein, mouse; D020346:Aquaporins