Coexpression of PMP22 gene with MBP and P0 during de novo myelination and nerve repair

Abstract

The recently cloned PMP22 gene, the rat variant of the murine growth arrest‐specific gene gas3, encodes a new 22 kD integral membrane glycoprotein of peripheral myelin. By means of in situ hybridization and immunohistochemistry, we have (1) analyzed PMP22 expression in myelinated and nonmyelinated peripheral nerves, and (2) compared the spatio‐temporal changes in the expression of PMP22 mRNA with the expression of the 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 cultured Schwann cells maintained under different conditions of cell growth and 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 to nondetectable levels in the degenerating distal stump. When a demyelinated and axon‐free distal stump, as indicated by the lack of MBP and neurofilament immunoreactivity, was reanastomosed to its proximal counterpart, the coordinated reexpression of PMP22 and MBP succeeded axonal 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 strictly growth arrest‐specific in Schwann cells. In conclusion, the spatio‐temporal pattern of PMP22 gene expression in developing, injured, and regenerating peripheral nerve very closely resembles P₀ and MBP expression, indicating a mechanism of PMP22 gene regulation in Schwann cells that is similar or identical to that of established myelin genes.