Oligodendrocyte-specific gene expression in mouse brain: Use of a myelin-forming cell type–specific promoter in an adeno-associated virus
✍ Scribed by Hong Chen; Douglas M. McCarty; Andrew T. Bruce; Kunihiko Suzuki; Kinuko Suzuki
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 779 KB
- Volume
- 55
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
To explore the feasibility of cell type-specific gene expression in oligodendrocytes as a possible therapeutic approach for demyelinating diseases, the cell specificity, tissue specificity, and duration of gene expression were investigated using recombinant adenoassociated viral vectors (rAAV) carrying a green fluorescence protein (GFP) gene. Recombinant AAV vectors carrying either the myelin basic protein (MBP) promoter (rAAV-MBP-GFP) or the cytomegalovirus (CMV) immediate early promoter (rAAV-CMV-GFP) were semistereotactically injected into the brain of C57BL/6J mice. Injection of the rAAV-MBP-GFP vector into or near the corpus callosum resulted in high levels of GFP expression in white matter regions. Double immunostaining with cell-specific markers proved that these GFP-expressing cells were oligodendrocytes. Injection of the rAAV-MBP-GFP vector into gray matter rarely produced GFP expression. In contrast, injection of the rAAV-CMV-GFP vector resulted in few GFP-expressing cells in the white matter, with most of the GFP-expressing cells being neurons located in the cerebral cortex along the needle track. The expression of the GFP driven by the MBP promoter persisted for at least 3 months.