Uncoupling of myelin assembly and Schwann cell differentiation by transgenic overexpression of peripheral myelin protein 22

We have generated previously transgenic rats that overexpress peripheral my elin protein 22 (PMP22) in Schwann cells. In the nerves of these animals, S chwann cells have segregated with axons to the normal 1:1 ratio but remain arrested at the promyelinating stage, apparently unable to elaborate myelin sheaths. We have examined gene expression of these dysmyelinating Schwann cells using semiquantitative reverse transcription-PCR and immunofluorescen ce analysis. Unexpectedly, Schwann cell differentiation appears to proceed normally at the molecular level when monitored by the expression of mRNAs e ncoding major structural proteins of myelin. Furthermore, an aberrant coexp ression of early and late Schwann cell markers was observed. PMP22 itself a cquires complex glycosylation, suggesting that trafficking of the myelin pr otein through the endoplasmic reticulum is not significantly impaired. We s uggest that PMP22, when overexpressed, accumulates in a late Golgi-cell mem brane compartment and uncouples myelin assembly from the underlying program of Schwann cell differentiation.