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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. J. Neurosci. Res. 55:504–513, 1999.  © 1999 Wiley‐Liss, Inc.