Impaired development of the cerebellum in transgenic mice expressing the immediate-early protein IE180 of pseudorabies virus

Abstract

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 subsequently to the brain. PRV immediate-early protein (IE180) activates transcription of the PRV early and late genes, and other viral and cellular genes, and represses its own transcription. To examine specific effects of IE180 in neuropathogenicity, we have generated four transgenic mouse lines expressing IE180 in a tetracycline-regulated system. In the transgenic mouse lines, cerebellar symptoms such as ataxic gait, tremor and motor discoordination were observed. Histopathology of the cerebella in the transgenic mouse lines showing severe symptoms was remarkable for a failure of layer formation and a reduction in cerebellar size. These findings suggest that IE180 affects the cascade of gene expression for development of the murine cerebellum, resulting in the impairment of the cerebellar development and differentiation.