PREMATURE SCHWANN-CELL DIFFERENTIATION AND HYPERMYELINATION IN MICE EXPRESSING A TARGETED ANTAGONIST OF THE POU TRANSCRIPTION FACTOR SCIP

The transcription factor SCIP is expressed by immature neurons and Sch wann cells of the developing central and peripheral nervous systems, b ut this expression is largely extinguished when these cells fully diff erentiate. In immature Schwann cells in vitro, SCIP acts as a represso r of the myelin-specific genes that mark full differentiation. We have generated transgenic mice that express a dominant-negative antagonist of SCIP, specifically targeted to developing Schwann cells. This anta gonist-designated Delta SCIP-is transcriptionally inactive, but retain s full DNA-binding activity. Mice that express Delta SCIP exhibit a de bilitating peripheral neuropathy that results from developmentally adv anced Schwann cell differentiation, overexpression of myelin-specific gene products, and hypermyelination. These results suggest that SCIP f unctions as a transcriptional sensor of differentiation cues and there by regulates the time and place at which Schwann cells differentiate.