Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/24256
標題: Cav3.2 T型鈣離子通道基因剔除小鼠微陣列資料分析
Microarray Dataset Analysis of the Cav3.2 T-type Calcium Channel Knockout Mouse Strain
作者: 何宜霖
Ho, I-Lin
關鍵字: 鈣離子通道
calcium channels
微陣列晶片
學習與記憶
基因網路
成對樣本T檢定
線性迴歸
關聯階層式分群
microarray
learning and memory
genetic pathways
paired-samples T-Test
Linear Regression Analysis
Hierarchical Clustering
出版社: 資訊管理學系所
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摘要: 大腦內的各個腦區分別執掌不同的功能,其中的海馬負責空間記憶及短期記憶形成長期記憶。Cav3.2 T型鈣離子通道的開啟會觸發許多細胞內生物化學的反應,例如肌肉收縮、基因表達、神經傳導物質的釋放等。近期文獻指出,α1H T型 鈣離子通道在海馬中有高度表現,並造成依賴海馬相關的學習障礙缺陷。本研究中利用微陣列基因晶片,取得α1H T型鈣離子通道剔除小鼠在接受痕跡恐懼實驗前後的左右側海馬內之基因表達數據,進行成對樣本T檢定分析(Paired-Samples T-Test),確認小鼠於訓練前後左右兩側海馬內基因表現量具有顯著差異;再利用線性迴歸分析(Linear Regression Analysis)篩選出表現量顯著改變之標靶基因。接著,利用階層式分析(Hierarchical Clustering)找出尚未在醫學中被證實生物功能的NA(non-available)基因所屬分群,並透過基因資料庫比對標靶基因是否與海馬功能有所關聯,進而探討標靶基因對學習記憶之影響。研究結果顯示,α1H T型鈣離子通道剔除小鼠的右側海馬在接受訓練後基因表現量改變不大;記憶訓練則使左側海馬內基因表現量回復到α1H T型鈣離子通道未被剔除之野生型小鼠相似之水準,本論文之研究成果將為基礎醫學研究者未來針對這些標靶基因進行功能探討之可行方向。
Different brain areas are responsible for specific functions of learning and memory. Among them, the hippocampus plays an important role in forming spatial, episodic and long-term memory. The α1H T-type Ca channel (Cav3.2) triggers many intracellular biochemical events, including muscle contraction, gene expression or hormones and neurotransmitter secretion. It has been demonstrated that the α1H T-type Ca2+ channel (Cav3.2) is highly expressed in the hippocampus and where it plays a critical role in hippocampal‐dependent learning. This thesis analyzed genome-wide expression microarray datasets obtained from the hippocampi of either naive or trace fear conditioned-α1H T-type calcium channel knockout mice for changes of transcriptome. First, paired-samples t-test was adopted to confirm whether there were significant difference of gene expression before and after training exist. Next linear regression analysis was applied to single out targeting genes which displayed significant difference in gene expression. After that, hierarchical clustering was implemented to find the cluster of NA (non-available) genes whose biological functions have not been confirmed biologically. The target genes were then put into the genetic information system for a comparison of their association with the development of the hippocampus in an attempt to find out whether they affected learning and memory. The results indicated that the right hippocampus of naive α1H T-type calcium channel knockout mice showed significant number of differentially expressed genes. The significant number of differentially expressed genes in the left hippocampus can be reduced to close to Wild Type group. This thesis research will provide a promising direction for further functional studies of the filtered targeting genes.
URI: http://hdl.handle.net/11455/24256
其他識別: U0005-2607201223282300
文章連結: http://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-2607201223282300
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