期刊
NEURODEGENERATIVE DISEASES
卷 1, 期 6, 页码 255-265出版社
KARGER
DOI: 10.1159/000085064
关键词
Parkinson's disease; Promoter activity; Nigrostriatal system; alpha-Synuclein; Transgene
资金
- DFG
Two missense mutations (A53T and A30P) in the gene encoding the presynaptic protein alpha-synuclein (asyn) are associated with rare, dominantly inherited forms of Parkinson's disease (PD) and its accumulation in Lewy bodies and Lewy neurites. As an initial step in investigating the role of asyn in the pathogenesis of PD, we have generated C57BL/6 transgenic mice overexpressing the doubly mutated human asyn under the control of three different promoters; the chicken beta-actin (ch beta actin), the mouse tyrosine hydroxylase 9.6 kb (msTH) and the mouse prion protein (msprp). In this study we compared the regional and cellular expression pattern of the transgenic protein in the brain and peripheral organs of various transgenic mouse lines. Western blot analysis and immunohistochemistry consistently showed that all three promoters successfully drive the expression of the transgene. The msprp promoter was found to give the highest level of transgene expression. All promoters directed the expression into the brain and specific neuron types. However, the promoters differed with respect to (i) the expression pattern in peripheral organs, (ii) the number and (iii) the regional distribution of expressing cells in the brain. Furthermore, remarkable line-to-line variation of expression patterns was observed in mouse lines carrying the same construct. Future studies will analyze how the variations in transgene expression affect the pathogenesis in the animals. Copyright (C) 2004 S. Karger AG, Basel
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据