Two missense mutations (A53T and A30P) in the gene encoding the presynaptic protein α-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 β-actin (chβactin), 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.
© 2004 S. Karger AG, Basel
- Parkinson’s disease
- Promoter activity
- Nigrostriatal system
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Christine C. Stichel, PhD
Animal Physiology, Biology, ND5/132
Ruhr University Bochum
DE–44780 Bochum (Germany)
Tel. +49 234 3225829, Fax +49 234 3214189, E-Mail email@example.com
L.M. and X.Z. both contributed equally.
Received: July 7, 2004
Accepted after revision: November 14, 2004
Number of Print Pages : 11
Number of Figures : 5, Number of Tables : 1, Number of References : 44
Vol. 1, No. 6, Year 2004 (Cover Date: Released May 2005)
Journal Editor: R.M. Nitsch, Zürich; C. Hock, Zürich
ISSN: 1660–2854 (print), 1660–2862 (Online)
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