Oligodendrocyte-specific gene expression in mouse brain: use of a myelin-forming cell type-specific promoter in an adeno-associated virus.
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 adeno-associated 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.
Chen
H
H
Neuroscience Center, University of North Carolina, Chapel Hill 27599-7525, USA.
McCarty
D M
DM
Bruce
A T
AT
Suzuki
K
K
D000818:Animals; D001921:Brain / Q000378:metabolism*; D003587:Cytomegalovirus / Q000235:genetics; D000229:Dependovirus / Q000235:genetics*; D015870:Gene Expression; D017930:Genes, Reporter / Q000235:genetics; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D007202:Indicators and Reagents / Q000032:analysis; D008164:Luminescent Proteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D004676:Myelin Basic Protein / Q000235:genetics* / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism*; D011401:Promoter Regions, Genetic
D007202:Indicators and Reagents; D008164:Luminescent Proteins; D004676:Myelin Basic Protein; D049452:Green Fluorescent Proteins