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Open Access Highly Accessed Research article

Greatly attenuated experimental autoimmune encephalomyelitis in aquaporin-4 knockout mice

Lihua Li, Hua Zhang and AS Verkman*

Author Affiliations

Departments of Medicine and Physiology, University of California, San Francisco, California, USA

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BMC Neuroscience 2009, 10:94  doi:10.1186/1471-2202-10-94

Published: 6 August 2009

Abstract

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 (MOG35–55) 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.

Conclusion

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.