title: Temporal deletion ofAqp11in mice is linked to the severity of cyst-like disease.
abstract: Aquaporin 11 (AQP11) is a channel protein with unknown biological function that is expressed in multiple tissues, including the kidney proximal tubule (PT) epithelium. Constitutive deletion ofAqp11in mice (Aqp11-/-) results in early postnatal vacuolization in the PT and development of apparent cysts at 2 wk of age. Electron microscopy of adultAqp11-/-mouse PT cells revealed a dilated rough endoplasmic reticulum. These changes may cause renal failure and premature death. This study examined1) whether postnatal deletion ofAqp11affects PT injury and cyst formation,2) the temporal role ofAqp11deletion on cyst development, and3) the nature of apparent cysts. Tamoxifen-inducibleAqp11-/-mice were generated (Ti-Aqp11-/-). Deletion ofAqp11at postnatal days (P) P2, P4, P6, P8, and P12 was investigated. Deranged renal development, especially in kidney cortex, PT cell vacuolization, and apparent tubular cysts developed only in mice whereAqp11gene disruption was induced until P8.Aqp11gene deletion from P12 onward did not result in a clear deficiency in renal development, PT injury, or cyst formation. Intraperitoneal injection of biotinylated-dextran (10 kDa) into adult mice resulted in extensive endocytic dextran uptake in both cysticAqp11-/-and control PT epithelium, respectively. This suggests that apparent cysts are not membrane-enclosed structures but represent PT dilations. We conclude thatAqp11-/-mice develop cyst-like dilated proximal tubules without documented cysts at time of death.
authors: Department of Health Science and Technology, Aalborg University, Aalborg, Denmark; and.
authors: Michael
authors: http://orcid.org/0000-0001-5597-8880
authors: M
authors: Rützler
authors: Department of Health Science and Technology, Aalborg University, Aalborg, Denmark; and.|Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors: Aleksandra
authors: A
authors: Rojek
authors: Department of Health Science and Technology, Aalborg University, Aalborg, Denmark; and.
authors: Mads Vammen
authors: MV
authors: Damgaard
authors: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors: Arne
authors: http://orcid.org/0000-0002-2160-591X
authors: A
authors: Andreasen
authors: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors: Robert A
authors: RA
authors: Fenton
authors: Department of Health Science and Technology, Aalborg University, Aalborg, Denmark; and sn@hst.aau.dk.
authors: Søren
authors: S
authors: Nielsen
mesh_terms: D000818:Animals; D020346:Aquaporins / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D007690:Polycystic Kidney Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012720:Severity of Illness Index
chemical_list: C503878:Aqp11 protein, mouse; D020346:Aquaporins
keywords: aquaporin; cell polarity; conditional knockout; polycystic kidney disease; renal embryology; vacuoles