The specificity of the myelin basic protein gene promoter studied in transgenic mice

The myelin basic proteins (MBPs) are a family of polypeptides that are pred ominantly expressed in the nervous system where they play a major role in m yelination. We have generated four lines of transgenic mice carrying a tran sgene in which 1.34 kb of the 5'-flanking sequence of the mouse MBP gene wa s fused upstream of the coding region of the Escherichia coli lac Z gene in order to investigate developmental and tissue-specific expression of the M BP gene. Expression of both the lacZ transgene and the endogenous MBP gene followed a common developmental pattern in mouse brain. Transgene expressio n was detected in primary oligodendrocytes, but not in type 2 astrocytes. I n addition, the lacZ gene product was expressed in epithelial cells of cert ain nonneural tissues, namely kidney, epididymis, ureter, and seminal vesic les. The ectopic expression of the transgene was associated with the develo pment of DNase I hypersensitive sites at the site of insertion which was fo und to be within the intron I region of the endogenous MBP gene. The result s reported here strongly suggest that the 1.34-kb 5'-flanking region of the MBP gene contains cis-regulatory elements that confer developmental regula tion of the MBP gene, although this region appears to lack elements that re strict its expression to the nervous system. (C) 2001 Academic Press.