Neuropathogenic abnormalities in transgenic mice expressing transcription factors of neurotropic viruses in the central nervous system

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To assess the neuropathogenic potentials of transcription factors of neurotropic viruses, we have generated several transgenic mouse lines.Pseudorabies virus (PRV) infection in animals other than its natural host almost always gives rise to fatal diseases in the central nervous system as a result of infection of peripheral neurons and subsequent to the brain. To study the role of immediate-early protein (IE180) of PRV in neuropathogenicity, we have generated transgenic mouse lines expressing IE180 in a tetracycline-regulated system (Tet-Off System). The transgenic mice showed cerebellar symptoms such as ataxic gait, tremor and motor discoordination. In the transgenic mice, histopathology of the cerebellum was remarkable for a failure of layer formation and reduced cerebellum sizes. Although the IE180 transcripts were detected in all tissues, no histological abnormality was observed in the tissues other than cerebellum. These findings suggest that IE180 affects the cascade of gene expression for development of the murine cerebellum.Borna disease virus infection causes a spectrum of behavioral deficits. To study the role of p24 of BDV in neuropathogenicity, we have generated transgenic mouse lines expressing p24 in astrocytes. The transgenic mice showed enhanced intermale aggressiveness and abnormalities in spatial learning. In the transgenic mice, brain-derived neurotrophic factor and synaptophysin were markedly decreased in hippocampus and cerebellum. These findings suggest that expression and accumulation of p24 in astrocytes creates neurodevelopmental disturbances.