COEXPRESSION OF PMP22 GENE WITH MBP AND P(O) DURING DE-NOVO MYELINATION AND NERVE REPAIR

The recently cloned PMP22 gene, the rat variant of the murine growth a rrest-specific gene gas3, encodes a new 22 kD integral membrane glycop rotein of peripheral myelin. By means of in situ hybridization and imm unohistochemistry, we have (1) analyzed PMP22 expression in myelinated and nonmyelinated peripheral nerves, and (2) compared the spatio-temp oral changes in the expression of PMP22 mRNA with the expression of th e myelin genes P0 and MBP (myelin basic protein) in developing as well as degenerating and regenerating sciatic nerve of rat. (3) We further investigated the expression of PMP22 mRNA by Northern blot in culture d Schwann cells maintained under different conditions of cell growth a nd arrest. Expression of PMP22 mRNA is restricted to Schwann cells of myelinated peripheral nerve. Transection of sciatic nerve in adult rat leads to a simultaneous and rapid decline in both PMP22 and P0 mRNA t o nondetectable levels in the degenerating distal stump. When a demyel inated and axon-free distal stump, as indicated by the lack of MBP and neurofilament immunoreactivity, was reanastomosed to its proximal cou nterpart, the coordinated reexpression of PMP22 and MBP succeeded axon al regeneration through the distal segment with a delay of 1-2 weeks. As in regenerating nerve, a striking synchrony of expression of PMP22 and P0 transcripts, as well as MBP immunoreactivity, could be observed during sciatic nerve development. Further, in vitro evidence suggests that, unlike NIH3T3-fibroblasts, expression of PMP22/gas3 is not stri ctly growth arrest-specific in Schwann cells. In conclusion, the spati o-temporal pattern of PMP22 gene expression in developing, injured, an d regenerating peripheral nerve very closely resembles P0 and MBP expr ession, indicating a mechanism of PMP22 gene regulation in Schwann cel ls that is similar or identical to that of established myelin genes. ( C) 1993 Wiley-Liss, Inc.