The expression of myelin basic protein exon 1 and exon 2 containing transcripts during myelination of the neonatal rat spinal cord--an in situ hybridization study

Abstract

During myelination, myelin proteins are expressed in a highly coordinated sequence. Of the four major isoforms of myelin basic protein, the proportion of the 21.5kDa and 17 kDa isoforms (which contain sequences encoded by myelin basic protein [MBP] exon 2) is enriched during active myelination in the mouse, suggesting that the alternative splicing of MBP transcripts containing exon 2 information is developmentally regulated. In this study, we compare the expression of MBP exon 1 and MBP exon 2 mRNAs in the neonatal rat spinal cord to establish whether developmental regulation of exon 2 mRNAs occurs in the rat in a manner similar to that previously described in the mouse. The expression of MBP mRNAs, together with that of proteolipid protein (PLP/DM-20) mRNA, in the developing white matter tracts increased dramatically between P7 and P10, corresponding to an increase in the extent of myelination. High levels of expression of each mRNA species examined were maintained between P10 and P14 as myelination proceeded. At P21, the expression of MBP exons 1 and 2 was reduced in the ventrolateral funiculi but was maintained at high levels in the dorsal funiculus. At P45, a further downregulation of both MBP mRNAs was apparent. By contrast, high levels of PLP/DM-20 expression were maintained from P10 onwards. In the grey matter, expression of MBP and PLP/DM-20 mRNAs increased more gradually and peak expression occurred later than in the white matter tracts. In this study, we therefore provide a description of myelin protein gene expression during post-natal development of the rat spinal cord. We have also shown that in the rat spinal cord, changes in the levels of MBP exon 2 expression associated with myelination reflect the changes of all MBP transcripts.