1. NCHU Institution Repository
  2. 管理學院
  3. 資訊管理學系
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
引用: 中文文獻 [1] 沈哲緯、劉怡均博士(2007), “Hippocampal-dependent learning of mice deficient in α1H T-type calcium channel”, 慈濟大學人類遺傳學研究所 [2] 王詩惠、蔡孟勳博士(2011), A hybrid genetic analysis system for mice brain microarray datasets, 中興大學基因體暨生物資訊學研究所 [3] 張春興，現代心理學，東華(1993) [4] 王克先著，學習心理學，桂冠圖書(1996) [5] 林惠玲、陳正倉，基礎統計學觀念與應用，雙葉書廊(2004) 382頁 英文文獻 [6] Schena, M., Shalon, D., Davis, R.W., Brown, P.O., “Quantitative monitoring of gene expression patterns with a complementary DNA microarray.”, Science 1995; 270 : 467-70 [7] Ross, D.T., Scherf, U., Eisen, M.B., Perou, C.M., Rees, C., Spellman, P., et al., “Systematic variation in gene expression patterns in human cancer cell lines”, Nat. Genet 2000; 24:227-235. [8] Fuster, J. M., “Memory and planning: Two temporal perspectives of frontal lobe function.” Adv. Neurol. 1995; 66, 9-19. [9] O’Keefea and Dostrovsky, 1971; Morris RG et al., 1982; D’Hooge and De Deyn, 2011 [10] Ghosh and Greenberg, 1995; Santella and Carafoli, 1997; Marks, 1997; Berridge, 1997, 1998; Berridgeet al., 2000 [11] Arvind K. Virmani, Jeffrey A. Tsou, Kimberly D. Siegmund, Linda Y. C. Shen, Tiffany I. Long, Peter W. Laird, Adi F. Gazdar, Ite A. Laird-Offringa, “Hierarchical Clustering of Lung Cancer Cell Lines Using DNA Methylation Markers”, Cancer Epidemiology, Biomarkers & Prevention 2002; 11:291–297. [12] Kaltschmidt B., Uherek M., Volk B., Baeuerle P.A., Kaltschmidt C., “Transcription factor NF-kappaB is activated in primary neurons by amyloid beta peptides and in neurons surrounding early plaques from patients with Alzheimer disease.” Proc. Natl. Acad. Sci. USA. 1997;94:2642–2647. [13] Hunot S., Brugg B., Ricard D., Michel P.P., Muriel M.P., Ruberg M., Faucheux B.A., Agid Y., Hirsch E.C., “Nuclear translocation of NF-kappaB is increased in dopaminergic neurons of patients with parkinson disease.” Proc. Natl. Acad. Sci. USA. 1997;94:7531–7536. [14] Khoshnan A., Ko J., Watkin E.E., Paige L.A., Reinhart P.H., Patterson P.H., “Activation of the IkappaB kinase complex and nuclear factor-kappaB contributes to mutant huntingtin neurotoxicity.” J. Neurosci.2004;24:7999–8008. [15] Orianne Philippe, Marlene Rio, Astrid Carioux, Jean-Marc Plaza, Philippe Guigue, Florence Molinari, Nathalie Boddaert, Christine Bole-Feysot, Patrick Nitschke, Asma Smahi, Arnold Munnich, and Laurence Colleaux, ”Combination of Linkage Mapping and Microarray-Expression Analysis Identifies NF-κB Signaling Defect as a Cause of Autosomal-Recessive Mental Retardation”, Am J Hum Genet. 2009 December 11; 85(6): 903–908. [16] Yong-Yeon Cho, “A novel role of brain-type ACS4 isotype in neuronal differentiation”, Biochemical and Biophysical Research Communications Volume 419, Issue 3, 16 March 2012, Pages 505–510 [17] Marc Sultan, Ilaria Piccini, Daniela Balzereit, Ralf Herwig,1 Nidhi G Saran, Hans Lehrach, Roger H Reeves, and Marie-Laure Yaspo, ”Gene expression variation in Down''s syndrome mice allows prioritization of candidate genes”, Genome Biol. 2007; 8(5): R91.Published online 2007 May 25. [18] Vannahme C, Smyth N, Miosge N, Gosling S, Frie C, Paulsson M, Maurer P, Hartmann U, ”Characterization of SMOC-1, a novel modular calcium-binding protein in basement membranes.”, J Biol Chem. 2002 Oct 11;277(41):37977-86. Epub 2002 Jul 18. [19] Wakisaka Y, Furuta A, Masuda K, Morikawa W, Kuwano M, Iwaki T., ”Cellular Distribution of NDRG1 Protein in the Rat Kidney and Brain During Normal Postnatal Development”, J Histochem Cytochem. 2003 Nov;51(11):1515-25. [20] Luo Y, Long JM, Lu C, Chan SL, Spangler EL, Mascarucci P, Raz A, Longo DL, Mattson MP, Ingram DK, Weng NP., ”A link between maze learning and hippocampal expression of neuroleukin and its receptor gp78.”, J Neurochem. 2002 Jan;80(2):354-61. [21] Li Z, Cui G, Wang J, Yu Z, Zhao L, Lv Z., ”Nemo-like kinase (NLK) involves in neuronal apoptosis after traumatic brain injury.”, Cell Mol Neurobiol. 2012 Apr;32(3):381-9. doi: 10.1007/s10571-011-9766-2. Epub 2011 Nov 30. [22] Min-Ching, Hsu(2003), “Regulatory Mechanisms of Growth-Associated Protein 43 (GAP-43) Expression and Phosphorylation in Developing Neurons”, Taipei Medical University Graduate Institute of Medical Sciences [23] A.J.G.D. Holtmaat et al., ”Directed expression of the growth-associated protein B-50/GAP-43 to olfactory neurons in transgenic mice results in changes in axon morphology and extraglomerular fiber growth”, J. Neurosci., 15 (1995), pp. 7953–7965 [24] Yu-Ting, Hsu(2006), “Protein-Protein Interaction of GAP-43 and Gephyrin in Developing Cortical Neurons”, Taipei Medical University Graduate Institute of Medical Sciences [25] L.I. Benowitz, A. Routtenberg, ”A membrane phosphoprotein associated with neural development, axonal regeneration, phospholipid metabolism, and synaptic plasticity”, Trends Neurosci., 10 (1987), pp. 527–532 [26] Benowitz LI, Routtenberg A., ”GAP-43: an intrinsic determinant of neuronal development and plasticity”, Trends in Neurosciences Volume 20, Issue 2, 1 February 1997, Pages 84–91 [27] Jerome L. Rekart, Karina Meiri, Aryeh Routtenberg, “Hippocampal-dependent memory is impaired in heterozygous GAP-43 knockout mice”, Hippocampus Volume 15, Issue 1, pages 1–7, 2005"
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
Appears in Collections:資訊管理學系

Show full item record
 
TAIR Related Article

Google ScholarTM

Check


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.