小腦脊髓萎縮症十二型 (Spinocerebellar ataxia 12, SCA12)是一種自體顯性遺傳疾病，目前在歐洲人和印地安人有病例發生。臨床徵兆有講話困難、小腦與周邊神經的病變、衰退，並伴隨著震顫的出現。SCA12是在基因PPP2R2B基因5’端CAG擴增所造成，也是目前在各型SCA疾病中所僅知功能基因5’端未轉錄部分擴增造成之結果，PPP2R2B基因會轉譯出一個專一表現在腦部的去磷酸PP2A (protein phosphotase 2A)的調控次單位Bβ。PP2A主要由三個次單元組成的Ser/Thr phosphatase，其組成次單元分別為A (結構次單元)、B (調控次單元)、C (催化單元)，而B次單元可以調控PP2A的生理角色進而調控很多細胞的功能，包含細胞週期的調控、tau的磷酸化和細胞自殺。CAG擴增的致病長度為55~78，而9~28是屬於正常範圍，而CAG的擴增被認為可能會影響到去磷酸酶的活性，進而改變蛋白質的磷酸化程度，使得細胞的正常功能失調。因此我們建立過量表現Bβ1的誘導細胞株和基因轉殖小鼠去測試這個假設。在動物模式中，我們已經得到異型核子與同型核子的基因轉殖小鼠並進行Rota-rod、locomotor和HomeCageScan之行為測試。總結，過量表現PPP2R2B基因引起基因轉殖小鼠的小腦病變包含了Purkinje cell 與神經細胞的缺少和神經膠化現象發生。其中也發現有情緒上的改變進而影響小鼠的行為表現之現象。為了測試過量表現Bβ1對細胞的影響，我們透過西方點墨法（western blot analysis）、細胞存活率測試（MTT assay）和細胞型態觀察來鑑定這些誘導細胞株。在加入氧化壓力藥物之後，轉入過量表現Bβ1的細胞株存活率明顯低於控制組，顯示細胞會因氧化壓力而導致凋亡。根據我們的研究顯示，過量表現Bβ1在我們的動物與細胞模式中，確實會造成神經細胞的毒性，而進一步導致神經凋亡。

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