title: Disruption of aquaporin-11 produces polycystic kidneys following vacuolization of the proximal tubule.
abstract: 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.
authors.affiliation: Department of Nephrology and Anatomy, Jichi Medical School, Tochigi, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Morishita
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Matsuzaki
authors.forename: Mariko
authors.initials: M
authors.lastname: Hara-chikuma
authors.forename: Ayaka
authors.initials: A
authors.lastname: Andoo
authors.forename: Mariko
authors.initials: M
authors.lastname: Shimono
authors.forename: Asako
authors.initials: A
authors.lastname: Matsuki
authors.forename: Katsuki
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ikeda
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Alan
authors.initials: A
authors.lastname: Verkman
authors.forename: Eiji
authors.initials: E
authors.lastname: Kusano
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ookawara
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Takata
authors.forename: Sei
authors.initials: S
authors.lastname: Sasaki
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ishibashi
mesh_terms: 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*
chemical_list: C503878:Aqp11 protein, mouse; D020346:Aquaporins