{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Yang B"],"funding":["NIBIB NIH HHS","NEI NIH HHS","NIDDK NIH HHS","NHLBI NIH HHS"],"pagination":["15280-6"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC2397463"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["283(22)"],"pubmed_abstract":["Aquaporin-4 (AQP4) is a water transport protein expressed in glial cell plasma membranes, including glial cell foot processes lining the blood-brain barrier. AQP4 deletion in mice reduces cytotoxic brain edema produced by different pathologies. To determine whether AQP4 is rate-limiting for brain water accumulation and whether altered AQP4 expression, as occurs in various pathologies, could have functional importance, we generated mice that overexpressed AQP4 in brain glial cells by a transgenic approach using the glial fibrillary acid protein promoter. Overexpression of AQP4 protein in brain by approximately 2.3-fold did not affect mouse survival, appearance, or behavior, nor did it affect brain anatomy or intracranial pressure (ICP). However, 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. In contrast, ICP elevation was 14 +/- 2 mmHg at 10 min in control mice and 9.8 +/- 2 mmHg in AQP4 knock-out mice. The deduced increase in brain water content correlated linearly with brain AQP4 protein expression. We conclude that AQP4 expression is rate-limiting for brain water accumulation, and thus, that altered AQP4 expression can be functionally significant."],"journal":["The Journal of biological chemistry"],"pubmed_title":["Glial cell aquaporin-4 overexpression in transgenic mice accelerates cytotoxic brain swelling."],"pmcid":["PMC2397463"],"funding_grant_id":["EY 13574","EB 00415","HL 73856","DK 72517","DK 35124","HL 59198"],"pubmed_authors":["Zador Z","Verkman AS","Yang B"],"additional_accession":[]},"is_claimable":false,"name":"Glial cell aquaporin-4 overexpression in transgenic mice accelerates cytotoxic brain swelling.","description":"Aquaporin-4 (AQP4) is a water transport protein expressed in glial cell plasma membranes, including glial cell foot processes lining the blood-brain barrier. AQP4 deletion in mice reduces cytotoxic brain edema produced by different pathologies. To determine whether AQP4 is rate-limiting for brain water accumulation and whether altered AQP4 expression, as occurs in various pathologies, could have functional importance, we generated mice that overexpressed AQP4 in brain glial cells by a transgenic approach using the glial fibrillary acid protein promoter. Overexpression of AQP4 protein in brain by approximately 2.3-fold did not affect mouse survival, appearance, or behavior, nor did it affect brain anatomy or intracranial pressure (ICP). However, 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. In contrast, ICP elevation was 14 +/- 2 mmHg at 10 min in control mice and 9.8 +/- 2 mmHg in AQP4 knock-out mice. The deduced increase in brain water content correlated linearly with brain AQP4 protein expression. We conclude that AQP4 expression is rate-limiting for brain water accumulation, and thus, that altered AQP4 expression can be functionally significant.","dates":{"release":"2008-01-01T00:00:00Z","publication":"2008 May","modification":"2025-04-04T19:30:30.934Z","creation":"2019-03-27T00:15:17Z"},"accession":"S-EPMC2397463","cross_references":{"pubmed":["18375385"],"doi":["10.1074/jbc.M801425200","10.1074/jbc.m801425200"]}}