博士 / 國防醫學院 / 生命科學研究所 / 97 / Synuclein was first indentified in cholinergic presynaptic vesicles from Torpedo californica. It has been kwon that human synuclein family consists of α-, -, and -synucleins. Only α-synuclein has been implicated in the pathogenesis of neurodegenerative diseases, for example, parkinson’s disease, dementia with Lewy body, multiple system atrophy and Alzheimer disease. -Synuclein has the function in the vesicle trafficking. -Synuclein plays an important role in tumorigenesis and tumor progression, it also has another role in the formation of glaucoma.
In this study, we identified and characterized three synuclein-related genes, which encode -,1-, and 2-synucleins, but no α-synuclein from zebrafish. By RT-PCR and whole-mount in situ hybridization, we demonstrated that sncb and sncga mRNA level were high in most brain tissues and spinal cord, while sncgb mRNA level was low in dorsal diencephalon. The 1.8-kb 5’-upstream/promoter region of the sncga gene was sufficient to direct robust GFP expression in the CNS and cranial ganglions. A transgenic line, Tg(sncga:GFP), was generated by Tol2-mediated transgenesis. The distribution of GFP signal is similar to endogenous expression pattern of sncga mRNA, but also includes the habenular complex. The bilateral habenular nuclei, efferent axons and the interpeduncular nucleus can be visualized by expression of GFP in the transgenic larva. This transgenic line can be applied for the study of left-right asymmetries in zebrafish brain in the future.
In order to establish the zebrafish model for the study of human Parkinson’s disease, wild-type and mutant forms of human -synuclein were expressed under the control of the regulatory fragments of HuC and TH1 promoter. By using Tol2-mediated transgenesis, several transgenic lines expressing wild-type and mutant forms of human -synuclein were generated. However, these lines did not show any symptoms related to Parkinson’s disease. In addition, the MPP+ toxicity did not cause significant loss of the TH1-positive neurons in the brain of these lines. These data indicate that these lines can not represent Parkinson’s disease model properly. Further studies will be performed to investigate any other factor is required to trigger Parkinson’s disease.
| Identifer | oai:union.ndltd.org:TW/097NDMC0105010 |
| Date | January 2009 |
| Creators | Yi-Chung Chen, 陳宜群 |
| Contributors | Chang-Jen Huang, 黃銓珍 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 64 |
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