Disease relevance of Aqp4

• In the Aqp4 deficient mouse, cochlear dysfunction is suggested as the primary cause of hearing impairment in the absence of neural conduction abnormality [1].
• We used mice deficient in each of the three principal lung aquaporins, AQP1, AQP4 and AQP5, to test the hypothesis that aquaporins are important in neonatal lung fluid balance, adult lung fluid clearance and formation of lung oedema after acute lung injury [2].
• In the brain, deletion of AQP4 conferred marked protection from brain swelling induced by acute water intoxication and ischaemic stroke [3].
• For example, in kidney, deletion of AQP1 or AQP3 produced marked polyuria whereas AQP4 deletion produced only a mild concentrating defect [3].
• Characterization of aquaporin-4 in muscle and muscular dystrophy [4].
• Following acute water intoxication produced by intraperitoneal water injection, AQP4-overexpressing mice had an accelerated progression of cytotoxic brain swelling, with ICP elevation of 20 +/- 2 mmHg at 10 min, often producing brain herniation and death [5].

Psychiatry related information on Aqp4

• Increased expression of water channel aquaporin 1 and aquaporin 4 in Creutzfeldt-Jakob disease and in bovine spongiform encephalopathy-infected bovine-PrP transgenic mice [6].
• For this purpose, both wild-type and AQP4 knockout mice were used with locomotor activity evaluation and microdialysis methods [7].

High impact information on Aqp4

• In another model of brain edema, focal ischemic stroke produced by middle cerebral artery occlusion, AQP4-deficient mice had improved neurological outcome [8].
• Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke [8].
• Here we show that NMO-IgG binds selectively to the aquaporin-4 water channel, a component of the dystroglycan protein complex located in astrocytic foot processes at the blood-brain barrier [9].
• IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel [9].
• We previously studied the role of AQP1 and AQP4 in lung fluid transport using knockout mice [10].

Chemical compound and disease context of Aqp4

• At 50 mg/kg PTZ, both groups exhibited seizure activity; however, the latency to generalized (tonic-clonic) seizures was significantly lower in wild-type than AQP4 mice [11].
• The results reveal that AQP4 deletion attenuated locomotor activity in acute and repeated cocaine exposure mice, and induced a decrease of extracellular dopamine and glutamate levels in the nucleus accumbens (NAc), a brain region known to be critically involved in the addictive properties of cocaine [7].

Biological context of Aqp4

• This region contains the neurological mutation ataxia, but further analysis reveals that Aqp4 is not responsible for the ataxia phenotype [12].
• Here we report the isolation and characterization of the cDNA for mouse Aqp4 and map the gene to the proximal region of mouse chromosome 18 [12].
• Aquaporin 4 (Aqp4), a member of a family of water transport proteins, is a candidate for playing a critical role in inner ear fluid homeostasis [1].
• Aqp4 knockout mice demonstrated impaired hearing, but normal neural conduction time [1].
• In the 5'-UTR of mouse and rat Aqp4 gene, sequence conservation was highest in the region spanning the transcription start site [1].

Anatomical context of Aqp4

• A single Aqp4 isoform was expressed in a highly conserved pattern within the supporting epithelia surrounding the sensory cells of the auditory and vestibular sensory organs and the glial cells surrounding the auditory nerve of the mouse and rat [1].
• Similar Aqp4 expression pattern and regulatory sequence conservation across species suggest a highly conserved role for Aqp4 in the inner ear [1].
• AQP4 may facilitate rapid osmotic equilibration in epithelial cells in the organ of Corti, which are subject to large K(+) fluxes during mechano-electric signal transduction [13].
• AQP5 immunolabeling was detected in the apical membranes of the acinus and duct cells, while AQP4 was expressed in the basolateral membranes only [14].
• Ultrastructural localization of aquaporin 4 and alpha1-syntrophin in the vascular feet of brain astrocytes [15].

Associations of Aqp4 with chemical compounds

• In contrast, the immunoreactivity of AQP4 was not affected by pilocarpine stimulation [14].
• Distribution of Aquaporin 4 in rodent spinal cord: relationship with astrocyte markers and chondroitin sulfate proteoglycans [16].
• The absence of H2 receptors-mediated signalling due to the inhibition of histamine release from ECL (enterochromaffin-like) cells by PYY may be in part responsible for the observed increase in the number of parietal cells expressing AQP4 [17].
• Immunocytochemistry revealed strong expression of aquaporin water channel AQP5 at the luminal membrane of serous epithelial cells in submucosal glands throughout the mouse nasopharynx and upper airways and AQP4 at the contralateral basolateral membrane in some glands [18].
• Between 7 and 15 d of age, distinct AQP4 immunoreactivity appeared in the S3 segment of the mouse proximal tubule concomitant with the differentiation of this segment of the nephron [19].

Other interactions of Aqp4

• Lung fluid transport in aquaporin-1 and aquaporin-4 knockout mice [20].
• Perivascular glial processes of the mdx mice appeared faintly stained by anti-AQP4 antibody, while in the controls a strong AQP4 labeling of glial processes was detected at light and electron microscope level [21].
• AQP4 expression has been reported to be absent at the sarcolemma and the perivascular astrocyte endfoot processes of alpha1-syntrophin knockout mice [15].
• AQP2 is specifically targeted to the apical cell domain, whereas AQP3 and AQP4 are expressed on the basolateral membrane [22].
• AQP3 and AQP4 are both present in the basolateral plasma membrane of collecting duct principal cells and represent exit pathways for water reabsorbed apically via AQP2 [23].

Analytical, diagnostic and therapeutic context of Aqp4

• Western blot analysis showed strong co-enrichment of the analyzed DAPs and AQP4, indicating that the membrane vesicle preparation was highly enriched in sarcolemma [24].
• To test this hypothesis, we investigated the ultrasturctural localization of AQP4 and alpha1-syntrophin in the brain astrocytes by using double immunogold labeled electron microscopy [15].
• Upper airway humidification, measured from the moisture gained by dry air passed through the upper airways in mice breathing through a tracheotomy, decreased from 91 to 50% with increasing ventilation from 20 to 220 ml/min, and reduced by 3-5% in AQP3/AQP4 knockout mice [25].
• In mice, however, AQP4 was also detected by immunocytochemistry in basolateral membranes of proximal tubule S3 segments, and not detected in S1 and S2 segments of proximal tubule [26].
• The role of aquaporin-4 in the blood-brain barrier development and integrity: studies in animal and cell culture models [27].

References