title: Glial-conditional deletion of aquaporin-4 (Aqp4) reduces blood-brain water uptake and confers barrier function on perivascular astrocyte endfeet.
abstract: Tissue- and cell-specific deletion of the Aqp4 gene is required to differentiate between the numerous pools of aquaporin-4 (AQP4) water channels. A glial-conditional Aqp4 knockout mouse line was generated to resolve whether astroglial AQP4 controls water exchange across the blood-brain interface. The conditional knockout was driven by the glial fibrillary acidic protein promoter. Brains from conditional Aqp4 knockouts were devoid of AQP4 as assessed by Western blots, ruling out the presence of a significant endothelial pool of AQP4. In agreement, immunofluorescence analysis of cryostate sections and quantitative immunogold analysis of ultrathin sections revealed no AQP4 signals in capillary endothelia. Compared with litter controls, glial-conditional Aqp4 knockout mice showed a 31% reduction in brain water uptake after systemic hypoosmotic stress and a delayed postnatal resorption of brain water. Deletion of astroglial Aqp4 did not affect the barrier function to macromolecules. Our data suggest that the blood-brain barrier (BBB) is more complex than anticipated. Notably, under certain conditions, the astrocyte covering of brain microvessels is rate limiting to water movement.
authors: Centre for Molecular Medicine Norway, Nordic EMBL Partnership,  University of Oslo, 0318 Oslo,  Norway.
authors: Nadia Nabil
authors: NN
authors: Haj-Yasein
authors: Gry Fluge
authors: GF
authors: Vindedal
authors: Martine
authors: M
authors: Eilert-Olsen
authors: Georg Andreas
authors: GA
authors: Gundersen
authors: Øivind
authors: Ø
authors: Skare
authors: Petter
authors: P
authors: Laake
authors: Arne
authors: A
authors: Klungland
authors: Anna Elisabeth
authors: AE
authors: Thorén
authors: John Michael
authors: JM
authors: Burkhardt
authors: Ole Petter
authors: OP
authors: Ottersen
authors: Erlend Arnulf
authors: EA
authors: Nagelhus
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics* / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000378:metabolism*; D015153:Blotting, Western; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D014867:Water / Q000378:metabolism*
chemical_list: C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D014867:Water