臺灣博碩士論文加值系統

腫瘤易感性基因tsg101為1996年由史丹佛大學之Stanley Cohen實驗室所發現，在胚胎組織與癌組織中可發現許多剪接異常之產物。由文獻指出，tsg101具有參與MDM2/p53回饋機制、細胞內蛋白質傳送、以及調控細胞增殖與分化之角色。已知tsg101為胚胎發育早期所必須，tsg101缺乏會導致中胚層無法形成，而導致胚胎無法正常發育。本實驗主要目的在觀察tsg101於小鼠胚胎發育各時期與成鼠腦部各組織表現之比較。藉由比較tsg101表現位置與器官發育之相互關係，以幫助瞭解tsg101在發育胚胎各時期中於不同組織所扮演的角色是否不同。結果顯示tsg101於早期廣泛的表現於胚胎組織中，隨著胚胎發育，則漸漸表現於E14.5的肺臟、小腸與腎臟等上皮組織中與甲狀腺、胸線與腎上腺等腺體組織中，顯示tsg101可能與tsg101與胚胎發育初期細胞快速增殖及發育後期上皮組織分化與腺體分泌之功能有關。此外，本研究觀察tsg101於成熟小鼠腦組織之表現情況，結果顯示tsg101在大腦皮質之椎狀細胞與星狀細胞，以及丘腦之黑色素細胞與小腦之浦金氏細胞有明顯表現。而這些細胞皆與腦內各類神經訊息傳導有關，是否tsg101與這些細胞內神經傳導物質傳輸之調控有相關則是一個值得探討的有趣研究主題。此外，意外發現thyroglobulin表現於大腦皮質之椎狀細胞與丘腦之黑色素細胞以及小腦之浦金氏細胞中，而thyroid transcription factor（TTF-1）表現於大腦皮質第VI層與丘腦之神經束中，thyroglobulin為甲狀腺特異性之蛋白，而TTF-1，則除了甲狀腺外，另在腦下垂體組織中亦會表現，文獻指出兩者皆會影響腦組織之發育，其在腦組織中之表現及所扮演的角色仍值得進一步加以釐清。

Mouse tumor susceptibility gene, tsg101, was discovered by Dr. Stanley Cohen at Stanford University in 1996. Subsequent studies have revealed multiple functions of tsg101. It participates in MDM2/p53 regulatory circuit, protein trafficking and regulation of cellular proliferation and differentiation. Knockout mouse experiment has demonstrated an essential role of tsg101 in early embryonic development, since tsg101 deficiency results in malformation of mesoderm, hence embryonic lethality. To further scrutinize the role of tsg101 in mouse tissues during the stages of organogenesis, we analyzed tsg101 protein steady state expression profile in the developing embryo. The data indicated that tsg101 was ubiquitously and diffusedly expressed in all early embryonic tissues, suggesting a role of tsg101 in rapid dividing early embryonic cells. Along the developmental path, tsg101 expressions became more specific in the epithelial cells of lung, intestine, kidney, thyroid, thymus and adrenal gland. This is concordant with previous report of tsg101 function in regulation of epithelial cell differentiation. In addition, tsg101 expression was found in pyramidal and stellate cells in cerebral cortex, substantia nigra cells of thalamus and Purkinje cells in cerebellum of adult mouse. Whether tsg101 participates in regulating the trafficking of neurotransmitters in these neuronal cells awaits further investigation. Surprisingly, we found congruous expression profile of thyroglobulin in these neuronal cells, except in stellate cells. Besides, the expression of TTF-1 was found in the VI layer of cerebral cortex and neuronal fiber in thalamus. Both thyroglobulin and TTF-1 are thyroid specific proteins, which are important for the development of brain tissues. Further investigation is urged to clarify whether these two proteins really present in these brain tissues and their functional role in these neuronal cells.

英文摘要 2
中文摘要 4
背景資料 5
材料方法 11
結果 23
討論 31
參考文獻 37
圖表 42
附圖 63

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