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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 林淑華 | |
dc.contributor.author | Hsien-Wei Hsieh | en |
dc.contributor.author | 謝獻緯 | zh_TW |
dc.date.accessioned | 2021-06-15T12:28:26Z | - |
dc.date.available | 2016-08-26 | |
dc.date.copyright | 2016-08-26 | |
dc.date.issued | 2016 | |
dc.date.submitted | 2016-08-08 | |
dc.identifier.citation | 參考文獻
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Autism and Intellectual Disability-Associated KIRREL3 Interacts with Neuronal Proteins MAP1B and MYO16 with Potential Roles in Neurodevelopment. PLoS One 10, e0123106 (2015). 64. Bhalla, K. et al. Alterations in CDH15 and KIRREL3 in patients with mild to severe intellectual disability. Am J Hum Genet 83, 703-13 (2008). 65. Park, J. & Moghaddam, B. Impact of anxiety on prefrontal cortex encoding of cognitive flexibility. Neuroscience (2016). 66. Molyneaux, B.J., Arlotta, P., Menezes, J.R. & Macklis, J.D. Neuronal subtype specification in the cerebral cortex. Nat Rev Neurosci 8, 427-37 (2007). 67. Konstantoudaki, X., Chalkiadaki, K., Tivodar, S., Karagogeos, D. & Sidiropoulou, K. Impaired synaptic plasticity in the prefrontal cortex of mice with developmentally decreased number of interneurons. Neuroscience 322, 333-45 (2016). | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/50042 | - |
dc.description.abstract | 微核醣核酸(microRNA)為物種間高度保留之非轉譯型小核醣核酸分子,具有轉錄後調控基因表現之功能。微核醣核酸-125b(miR-125b)為微核醣核酸-125b1及微核醣核酸-125b2經轉錄後修飾產生,高度表現於大腦及神經系統。在線蟲、果蠅及斑馬魚的微核醣核酸-125b剔除模型中皆顯示於個體發育及神經系統分化扮演重要角色。賈可森症候群(Jacobsen syndrome)為罕見染色體缺失疾病,又稱為11q缺失症候群,主要於人類11號染色體長臂23.3至末端(11q23.3-qter)發生部分缺失,造成大量基因刪除,導致許多生理病徵及行為異常,包括血小板數量減少及功能異常、生長遲緩、大腦異常等問題,也常伴隨學習認知障礙、自閉症類群障礙等行為缺失,至今仍無代表性單一基因剔除動物模型模擬賈可森症候群。微核醣核酸-125b1基因位於賈可森症候群染色體缺失區域,本論文利用Mir125b1單套基因剔除小鼠(Mir125b1+/-),分析其生理狀況及行為,評估其是否可成為賈可森症候群之動物模型。本研究發現Mir125b1+/- 10週齡小鼠體重較輕,進一步量測重要器官發現大腦重量明顯較輕,顯示Mir125b1+/-小鼠大腦及生長發育受到影響。經分析Mir125b1+/-小鼠全血無此症候群常見血小板不足病徵。在多套行為試驗中,Mir125b1+/-小鼠的活動能力、運動協調能力及社交行為無明顯異常,但有焦慮及易沮喪傾向,顯示Mir125b1+/-小鼠具有自閉症類群障礙傾向。另由於水迷津及巴恩斯迷宮試驗實驗結果互異,因此無法證實Mir125b1+/-小鼠是否具有空間記憶學習障礙。為分析Mir125b1+/-小鼠大腦與沮喪相關性,藉由量測大腦厚度發現Mir125b1+/- 18.5天胚胎及10週齡成鼠大腦皮質厚度皆較野生正常者薄。根據實驗結果,本論文證明Mir125b1+/-小鼠個體發育及大腦器官受到影響,並推估具有賈可森症候群的自閉症類群障礙表徵,可能成為此疾病代表之動物模型。 | zh_TW |
dc.description.abstract | MicroRNAs (miRNA) are polygenetically highly conserved small non-coding RNAs which regulate gene expression post-polygenetically. MicroRNA-125b (miR-125b) is generated from miR-125b1 and miR-125b2 and highly expressed in brain and neuron. MiR-125b plays an important role in the organism development and differentiation of the neuron system evidenced by many miR-125b knockout animal models including C. elegans, Drosophila and zebrafish.
Jacobsen syndrome (JS) is a rare chromosomal deletion disorder, also called 11q terminal deletion disorder. This disease is mainly caused by partial deletion of the long arm of chromosome 11 including the q23.3 to the end of 11q (11q23.3-qter) which results in multiple genes depletion and causes physiological and behavioral abnormalities such as thrombocytopenia, abnormal platelet function, growth retardation, and brain abnormality. Patients may have cognitive learning problem and autism spectrum disorder. There is no single gene knockout animal model mimicking Jacobsen syndrome until now. Since miR-125b1 gene is located in the deletion region of Jacobsen syndrome, the goal of this study is evaluating whether the Mir125b1 heterozygous knockout mice (Mir125b1+/- mice) can be an animal model of Jacobsen syndrome by analyzing the physical condition and the behavior of Mir125b1+/- mice. The weight of Mir125b1+/- 10 week-old mice were lower than their littermate controls groups. Moreover, by analyzing the weight of major organs, the brain weight of Mir125b1+/- mice were decreased compared with their control groups. These results implied the growth of the brain and weight of Mir125b1+/- mice may be affected. Although the platelet abnormality is commonly found in patients with Jacobsen syndrome, the PLT count of Mir125b1+/- mice did not show any significant difference. In multiple behavior tests, Mir125b1+/- mice showed normal mobility, motor coordinating ability, and social behavior; however, the anxiety and depression tendency of Mir125b1+/- mice were significantly increased. These results suggested that Mir125b1+/- mice might have autism spectrum disorder. On the other hand, the consequences of water maze and the barnes maze test were incompatible. It is still controversial whether Mir125b1+/- mice have the spatial learning and memorial problems. To establish the correlation of the deficit of cerebral cortex and depression in Mir125b1+/- mice, the thickness of cortical cortex in Mir125b1+/- E18.5 embryos and 10 week-old mice were measured and both were significantly thinner than their WT controls. In conclusion, my thesis proofed that Mir125b1+/- mice with reduced weight in body and brain and autism-like spectrum disorder behaviors, indicating Mir125b1+/- mice might be a potential animal model of Jacobsen syndrome. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T12:28:26Z (GMT). No. of bitstreams: 1 ntu-105-R01424016-1.pdf: 2669350 bytes, checksum: 77e0fd770ecf1483462581f2cb693ad9 (MD5) Previous issue date: 2016 | en |
dc.description.tableofcontents | 目錄
口試委員審定書 i 誌謝 ii 中文摘要 iii 英文摘要 iv 目錄 vi 圖目錄 viii 表目錄 ix 附錄目錄 x 第一章 緒論 1 第一節 微核醣核酸-125家族簡介 1 第二節 微核醣核酸-125b簡介及個體、神經發育相關研究 1 第三節 賈可森症候群 (Jacobsen syndrome)簡介及相關文獻 3 第四節 賈可森症候群 (Jacobsen syndrome)相關動物模型及近期研究 3 第五節 自閉症類群障礙(autism spectrum disorder)簡介 4 第六節 遺傳基因與微核醣核酸在自閉症類群障礙相關介紹 5 第七節 研究動機與策略 6 第二章 材料方法 7 第一節 實驗動物 (Experimental animals) 7 第二節 Mir125b1基因剔除小鼠組織去氧核醣核酸萃取與基因型鑑定 7 第三節 小鼠胚胎及成鼠大腦切片製備 8 第四節 尼氏染色法流程 (Nissl Stain) 8 第五節 曠野實驗 (Open field test) 9 第六節 旋轉滾筒平衡實驗 (Rotarod test) 9 第七節 社交行為測試 (Social interaction Test) 9 第八節 舉臂式十字迷宮 (Elevated plus maze) 10 第九節 尾部懸吊試驗 (Tail suspension test) 10 第十節 強迫游泳實驗 (Forced swimming test) 10 第十一節 水迷津 (Water maze) 10 第十二節 巴恩斯迷宫試驗 (Barnes maze) 11 第十三節 數據統計與分析 12 第三章 實驗結果 13 第一節 研究Mir125b1單套基因剔除鼠生理表徵 13 第二節 研究Mir125b1單套基因剔除鼠行為缺失 14 第三節 研究Mir125b1單套基因剔除鼠大腦結構 17 第四章 實驗討論 18 未來目標及展望 21 參考文獻 22 | |
dc.language.iso | zh-TW | |
dc.title | 探討微核醣核酸-125b1與賈可森症候群之關聯性 | zh_TW |
dc.title | Investigating the relationships between microRNA-125b1 and Jacobsen Syndrome | en |
dc.type | Thesis | |
dc.date.schoolyear | 104-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 黃祥博,胡忠怡,游益興 | |
dc.subject.keyword | 微核醣核酸-125b1,賈可森症候群,動物行為試驗,基因剔除鼠,自閉症類群障礙, | zh_TW |
dc.subject.keyword | microRNA-125b1,Jacobsen syndrome,animal behavior test,gene knockout mice,autism spectrum disorder, | en |
dc.relation.page | 53 | |
dc.identifier.doi | 10.6342/NTU201602086 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2016-08-08 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 醫學檢驗暨生物技術學研究所 | zh_TW |
顯示於系所單位: | 醫學檢驗暨生物技術學系 |
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