建立和分析過量表現PPP2R2B基因之基因轉殖小鼠

Establishment and analyses of PPP2R2B overexpression transgenic mice

林立昉(Li Fang Lin)

指導教授 ： 謝秀梅

國立臺灣師範大學/理學院/生命科學研究所/碩士(2005年)

摘要

無資料

關鍵字

自體顯性脊髓小腦共濟失調症 ； 脊髓小腦運動失調症第12型 ； 顯微注射 ； 企鵝家族

並列摘要

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.

並列關鍵字

PP2A ； PR55 ； ADCA ； SCA12 ； phosphatase 2A ； Neuron specific enolase ； microinjection ； PPP2R2B

參考文獻

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