Document Type
Article
Publication Date
1-1-2007
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.
Recommended Citation
Zhou, Hongxia; Falkenburger, Björn H; Schulz, Jörg B; Tieu, Kim; Xu, Zuoshang; and Xia, Xu Gang, "Silencing of the Pink1 gene expression by conditional RNAi does not induce dopaminergic neuron death in mice." (2007). Department of Pathology, Anatomy, and Cell Biology Faculty Papers. Paper 87.
https://jdc.jefferson.edu/pacbfp/87
PubMed ID
17389931
Comments
This article has been peer reviewed and is published in International Journal of Biological Sciences 2007 Mar 5;3(4):242-50. The published version is available at DOI: 10.7150/ijbs.3.242. ©Ivyspring International Publisher