Effect Of Lacking Prion-like Protein Shadoo On Neurobehavior In Mice

Prion diseases are a group of neurodegenerative diseases. Bovine spongiform encephalopathy (BSE), one of prion diseases, once ravaged British. It is also known as "Mad cow disease". Risk of suffering from prion diseases may be increased when BSE-infected beef enters our food chain. Thus, researches on prion diseases are beneficial to food security. Prion diseases are found to be formed by virtue of a conformational change involving the cellular prion protein (PrPC) turning to the scrapie prion protein (PrPSC) and deposited in the brain. The mechanism of prion diseases is still unknown. It was supposed that there is a protein "X" which may play a key role in the process of PrPC turning to PrPSC. Shadoo, a new member of prion family, shared a highly conserved hydrophobic region with PrPc. Like PrPc, Shadoo protein distribute in nervous system, and the two proteins may share a overlap neuroprotective function, indicating that Shadoo may be a candidate of protein "X". Researches on the function of Shadoo may contribute to the understanding of the mechanism of prion diseases.Behaviors, the respondence of animals reflect to environment or stimulation, are regulated by nervous system. The normal behavior of animals indicate the functional integrity of the nervous system, and any behavior changes reflect the status of the nervous system function.After a variety of behavior experiments, it confirmed that Sho0/0mice did better than wild type mice with improved spatial learning and memory and motor ability in Morris water maze, but not so active as wild type mice. The ability of explore and associative learning increased while Shadoo deficient(Sho0/0mice), but the effect was not obvious. Sho0/0mice were identified as mutation homozygote mice by PCR; Western blot detected that no Shadoo expressed in neither cerebrum nor cerebellum in Sho0/0mice, but PrPc increased in Sho0/0mice cerebrum and reduced in the cerebellum, when compared with wild type mice. Immunohistochemistry suggested no Shadoo was detected in Sho0/0mice brain. Besides, it was found that Shadoo protein is mainly expressed in the hippocampus of cerebrum and Purkinje cells of cerebellum. The result of two-dimensional electrophoresis and mass spectrum showed the24differential proteins between Sho0/0mice and wild type mice in the brain, which had at least2times variation of expression levels. In these24proteins,3 proteins up-regulated and18proteins down-regulated while the others totally unexpressed. Researches on the functional interrelationships of Shadoo proteins and those proteins may explain the change of neurobehavior in Sho0/0mice and thus contribute to the understanding of the functional role of Shadoo protein and the pathogenesis of prion diseases.