MODIFICATION OF SCHWANN-CELL PHENOTYPE WITH PLP TRANSGENES - EVIDENCETHAT THE PLP AND DM20 ISOPROTEINS ARE TARGETED TO DIFFERENT CELLULAR DOMAINS

The X-linked proteolipid protein (Plp) gene encodes PLP, the major pro tein of central nervous system myelin, and its alternative RNA splice product, termed DM20. Schwann cells also express the Plp gene but, in contrast to oligodendrocytes, neither protein is incorporated into per ipheral myelin, In the present study, we use different transgenes enco ding PLP and DM20 to modify the expression of these proteins in myelin -forming Schwann cells of wild-type and jimpy mice, Increasing the lev el of PLP, either singly or in combination with DM20, leads to the inc orporation of PLP into the compacted myelin sheath; however, DM20 alwa ys remains restricted to cytoplasmic regions of the Schwann cell, The insertion of PLP into the membrane does not appear to depend on a coop erativity of the two isoproteins, The presence of PLP does not visibly alter the ultrastructure and periodicity of peripheral nervous system (PNS) myelin, The results indicate that the absence of PLP in the per ipheral myelin of normal animals most probably reflects the very low a mounts of this isoprotein synthesised by Schwann cells, The preferenti al incorporation of PLP, as opposed to DM20, in peripheral myelin may indicate that a myelin targeting signal is present in the PLP-specific region of the molecule. (C) 1997 Wiley-Liss, Inc.