Identification of a cDNA coding for a fifth form of myelin basic protein in mouse.

Abstract

The primary sequences of four molecular mass variants (14, 17, 18.5, and 21.5 kDa) of the mouse myelin basic protein (MBP) have recently been determined through analysis of cDNA clones of their mRNAs. The mRNAs coding for the four MBP variants are thought to arise by differential splicing of two exons (exons 2 and 6) from a single gene. In contrast, exons 2 and 5 may be spliced out in the posttranscriptional processing of the human MBP gene. To investigate the possibility that a third exon (exon 5) may also be differentially spliced out in the processing of the mouse MBP gene transcript, a mouse cDNA library was screened to search for cDNAs missing exon 5. A MBP cDNA was isolated whose coding region specified a fifth mouse MBP variant with a molecular mass of approximately equal to 17 kDa. The mass of this variant (17,257 Da) is so close to that of the other 17-kDa mouse MBP (17,224 Da) that the two would be indistinguishable on NaDodSO4/polyacrylamide gels. Analysis of the sequence of the cDNA clone indicates that excision of exons 2 and 5 of the mouse MBP gene would produce the mRNA encoding this newly described 17-kDa MBP, whereas excision of exon 6 would produce the mRNA for the other 17-kDa MBP variant. Thus, the "17-kDa" mouse MBP consists of at least two molecular forms with very similar molecular masses but markedly different primary sequences. Of five full-length or near full-length cDNAs representing 17-kDa MBPs, one was missing exons 2 and 5 and four were missing exon 6.