The Proximal Region of the MBP Gene Promoter is Sufficient to Induce Oligodendroglial‐specific Expression in Transgenic Mice

To characterize regulatory DNA sequences involved in oligodendroglial expression of myelin basic protein (MBP), transgenic mice carrying a 256 bp fragment of the mouse MBP promoter fused to an Escherichia coli lacZ gene were generated. Of four transgenic families, two (lines 2 and 4) expressed β-galactosidase activity in the nervous system but not in most other tissues. Histochemical and immunohistochemical analysis of adult brain from these two lines showed oligodendroglial-specific expression of the transgene. In line 2, only a small proportion of oligodendrocytes expressed the transgene, and in labelled cells the product of the enzymatic reaction with β-galactosidase was confined to a small round vesicle in the vicinity of the nucleus. In contrast, in tissue sections from line 4 adult brain and spinal cord β-galactosidase activity was much more intense and at least 80 – 90% of oligodendrocytes expressed the transgene. Detection of the MBP-lacZ transcript by in situ hybridization showed that the transgene mRNA was confined to the oligodendrocyte cell body. These results suggest that cis-acting regulatory elements, specifying oligodendrocytes identity, are located within 256 bp upstream from the MBP gene.