Impaired development of the cerebellum in transgenic mice expressing the immediate-early protein IE180 of pseudorabies virus.
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.
Taharaguchi
Satoshi
S
Laboratory of Animal Experiment for Disease Model, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
Kon
Yasuhiro
Y
Yoshino
Saori
S
Ono
Etsuro
E
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D002531:Cerebellum / Q000196:embryology* / Q000378:metabolism / Q000473:pathology; D003605:D-Amino-Acid Oxidase / Q000235:genetics; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D020234:Gait Ataxia / Q000209:etiology; D015870:Gene Expression; D017874:Immediate-Early Proteins / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009024:Morphogenesis; D009043:Motor Activity; D009419:Nerve Tissue Proteins / Q000235:genetics; D010641:Phenotype; D019076:Transgenes
D002352:Carrier Proteins; C086936:Fabp7 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D017874:Immediate-Early Proteins; D009419:Nerve Tissue Proteins; C047583:pseudorabies virus immediate early proteins; D003605:D-Amino-Acid Oxidase