In this experimental model of EAE in C57/BL6 mice in which passively transferred IgG from NMO patients is infused at onset of neurologic disease, we conclude that the anti-AQP4 antibody contributes to the pathogenicity by targeting subpial astrocytes leading to large, confluent demyelinated lesions in the spinal cord and optic nerve. This evidence concerns the gene AQP4 and nervous system disorder.