Establishment and analyses of PPP2R2B overexpression transgenic mice

• Main Authors: Li Fang Lin, 林立昉
• Other Authors: Hsiu Mei Hsieh-Li
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/15593906913746262925

碩士 === 國立臺灣師範大學 === 生命科學研究所 === 94 === SCA12 is an autosomal dominant spinal cerebellar ataxia (SCA) disease. According to previous studies, it is caused by CAG repeat expansion of the 5’UTR of gene PPP2R2B and it is the only SCA that has CAG repeat expansion on the 5’UTR of disease-causing gene. The PPP2R2B gene encodes a brain-specific regulatory subunit Bβ of PP2A (protein phosphotase 2A) and CAG expansion is thought to effect its activity. We have established PPP2R2B overexpression stable cell line and transgenic mice in which GFP-fused transgene is driven by a neuron specific enolase (NSE) promoter. We found that cells with Bβ expression show reduce proliferation compared to vector-transfected cells during serum starvation. This result suggests that Bβ renders cells to be vulnerable to environmental stress. Of the mouse model, among the 10 founder lines, 8 lines were found to have GFP signals in the brains. Line-20 was observed to have transgene product expressed. Results from behavioral characterization have shown that these mice have significantly poor performance compare to their wild-type littermates in both beam test and rota-rod. By immunohistochemical analysis, we have also identified Purkinje cell loss in the cerebella of line 20 transgenic mice. We conclude that the overexpression of PPP2R2B causes the pathogenesis in the mouse cerebellum. Molecular mechanism of the pathogenesis needs to be further characterized.