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研究生:魏江庭
研究生(外文):Chiang-TingWei
論文名稱:額顳葉退化症小鼠模式之基因表達分析
論文名稱(外文):The global analysis of expressed genes in FTLD mouse model
指導教授:蔡坤哲蔡坤哲引用關係
指導教授(外文):Kuen-Jer Tsai
學位類別:碩士
校院名稱:國立成功大學
系所名稱:臨床醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2013
畢業學年度:101
語文別:英文
論文頁數:52
中文關鍵詞:額顳葉退化症小鼠模式基因表達分析
外文關鍵詞:frontotemporal lobar degenerationmouse modelgene-expression analysis
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額顳葉退化症(FTLD)是一種神經退化疾病,主要的特徵為患者腦部額葉與顳葉部分之神經元大量死亡。在具有泛素包含體之額顳葉退化症的患者腦中,TDP-43(TAR DNA binding protein-43)為構成具有神經毒性之細胞質及細胞核內包含體之主要蛋白。過去的文獻中指出,基因表現之失調可能與神經退化疾病包括額顳葉退化症之致病有關。本研究中嘗試使用CaMKII啟動子驅動之TDP-43基因轉殖鼠模擬額顳葉退化症致病機轉,作為額顳葉退化症之動物模式,進行額顳葉退化症小鼠模式腦部表現基因之全局分析,以期發現參與額顳葉退化症致病過程之新穎基因。在比較額顳葉退化症小鼠及正常小鼠之腦部基因表現後,根據與神經退化疾病之關聯性,transthyretin (TTR)被挑選以進行後續研究。TTR之表現量在額顳葉退化症小鼠中有上升的現象。在額顳葉退化症小鼠模式腦中,TTR與TDP-43包含體有共定位的現象,且TTR與TDP-43也有免疫共沉澱的現象。總括來看,在額顳葉退化症小鼠模式腦中TTR的表現量有上升的趨勢,且TTR與TDP-43之間存在有相互作用。實驗結果暗示了TTR在額顳葉退化症的致病機轉中,可能扮演某種角色。
Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disease which characterized by neuronal loss in frontal/temporal lobe of the brain. TAR DNA-binding protein-43 (TDP-43) was identified as the major component of the neurotoxic cytoplasmic and nuclear inclusions in brains of FTLD-U patients. Previous studies have revealed that gene dysregulation may be responsible for the pathogenesis of neurodegenerative diseases including FTLD. This thesis purposed to use CaMKII promoter-driven TDP-43 transgenic mice as FTLD mouse model to perform a global analysis of expressed genes and to elucidate novel genes involved in FTLD pathogenesis. In the comparison of gene-expression between FTLD mice and wild-type mice, transthyretin (TTR) was chosen as the candidate for further studies based on the correlations with neurodegenerative diseases. Expression level of TTR was upregulated in brains of FTLD mice. TTR was co-localized with TDP-43 inclusions and co-immunoprecipitated with TDP-43 in brains of FTLD mouse model. Taken together, TTR, which was upregulated in FTLD mice, interacted with TDP-43 and could play a role in FTLD pathogenesis.
中文摘要 1
Abstract 2
Acknowledgement 3
Contents 4
Background 5
Materials and Methods 16
Results 23
Discussion 28
References 34
Tables and Figure Legends 45
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