Production of Schwann cell lines using a regulated oncogene.

The process of myelination in the central and peripheral nervous systems has been well characterized morphologically by a variety of techniques. It is evident from these studies that, in the peripheral nervous system myelin formation is a multistep process. Clearly, a 1:1 relationship must be established with the axon, which is followed by formation of the basal lamina and eventually myelin. Because immortalized Schwann cell lines obtained using SV40 T antigen under the control of an inducible promoter have many properties of untransfected Schwann cells in culture, including their ability to form myelin in vitro, these cells will enable us to dissect more easily the process of myelination. Having successfully immortalized rat Schwann cells without affecting their ability to differentiate fully, we are applying this approach to generate analogous cell lines from the peripheral nerves of other species such as mouse and human. Unlike rat Schwann cells, there are no known mitogens for human and mouse Schwann cells, making it impossible to expand these cell populations. The ability to produce large numbers of human Schwann cells from nerve biopsy and to analyze their biochemical properties would be of enormous value in identifying the cellular abnormalities that result in demyelinating disease. Likewise, there are several mutant mouse strains with defects in myelin formation, and cell lines from these animals would facilitate our understanding of the process leading to dysmyelination.