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Int J Biol Sci 2007; 3(4):242-250. doi:10.7150/ijbs.3.242

Research Paper

Silencing of the Pink1 Gene Expression by Conditional RNAi Does Not Induce Dopaminergic Neuron Death in Mice

Hongxia Zhou1, Björn H Falkenburger2, Jörg B Schulz2, Kim Tieu3, Zuoshang Xu4, Xu Gang Xia1

1. Department of Pathology, Anatomy & Cell Biology, Thomas Jefferson University, 1020 Locust Avenue, Philadelphia, PA 19107, USA
2. Department of Neurodegeneration and Restorative Research, DFG Research Center Molecular Physiology of the Brain and Center of Neurological Disease, University of Göttingen, Waldweg 33, 37073 Göttingen, Germany
3. Department of Environmental Medicine and Center for Aging and Developmental Biology, University of Rochester, School of Medicine and Dentistry, 575 Elmwood Avenue, Rochester, NY 14642, USA
4. Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation St, Worcester, MA 01605, USA

Abstract

Transgenic RNAi, an alternative to the gene knockout approach, can induce hypomorphic phenotypes that resemble those of the gene knockout in mice. Conditional transgenic RNAi is an attractive choice of method for reverse genetics in vivo because it can achieve temporal and spatial silencing of targeted genes. Pol III promoters such as U6 are widely used to drive the expression of RNAi transgenes in animals. Tested in transgenic mice, a Cre-loxP inducible U6 promoter drove the broad expression of an shRNA against the Pink1 gene whose loss-of-functional mutations cause one form of familial Parkinson's disease. The expression of the shRNA was tightly regulated and, when induced, silenced the Pink1 gene product by more than 95% in mouse brain. However, these mice did not develop dopaminergic neurodegeneration, suggesting that silencing of the Pink1 gene expression from embryo in mice is insufficient to cause similar biochemical or morphological changes that are observed in Parkinson's disease. The results demonstrate that silencing of the PINK1 gene does not induce a reliable mouse model for Parkinson's disease, but that technically the inducible U6 promoter is useful for conditional RNAi in vivo.

Keywords: RNAi, transgenic RNAi, U6 promoter, Parkinson disease, PINK1, mice

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How to cite this article:
Zhou H, Falkenburger BH, Schulz JB, Tieu K, Xu Z, Xia XG. Silencing of the Pink1 Gene Expression by Conditional RNAi Does Not Induce Dopaminergic Neuron Death in Mice. Int J Biol Sci 2007; 3(4):242-250. doi:10.7150/ijbs.3.242. Available from http://www.ijbs.com/v03p0242.htm