Greatly attenuated experimental autoimmune encephalomyelitis in aquaporin-4 knockout mice.
BACKGROUND
The involvement of astrocyte water channel aquaporin-4 (AQP4) in autoimmune diseases of the central nervous system has been suggested following the identification of AQP4 autoantibodies in neuromyelitis optica, an inflammatory demyelinating disease.


RESULTS
We investigated the involvement of AQP4 in disease severity in an established mouse model of experimental autoimmune encephalomyelitis (EAE) produced by immunization with myelin oligodendrocyte glycoprotein (MOG 35-55) peptide. EAE was remarkably attenuated in AQP4 null mice compared to identically treated wildtype mice. Whereas most wildtype mice developed progressive tail and hindlimb paralysis, clinical signs were virtually absent in AQP4 null mice. Brain and spinal cords from AQP1 null mice showed greatly reduced mononuclear cell infiltration compared to wildtype mice, with relatively little myelin loss and axonal degeneration.


CONCLUSIONS
The reduced severity of autoimmune encephalomyelitis in AQP4 deficiency suggests AQP4 as a novel determinant in autoimmune inflammatory diseases of the central nervous system and hence a potential drug target.
Li
Lihua
L
Department of Medicine, University of California, San Francisco, California, USA. Lihua.Li@ucsf.edu
Zhang
Hua
H
Verkman
A S
AS
D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001323:Autoantibodies / Q000276:immunology; D001835:Body Weight; D001921:Brain / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins; D007150:Immunohistochemistry; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000276:immunology* / Q000378:metabolism
C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D001323:Autoantibodies; D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55)