EXPRESSION, PURIFICATION, AND ENCEPHALITOGENICITY OF RECOMBINANT HUMAN MYELIN OLIGODENDROCYTE GLYCOPROTEIN

Myelin oligodendrocyte glycoprotein (MOG), a putative autoantigen in m ultiple sclerosis (MS), is a quantitatively minor component of the CNS . In view of the difficulties associated with the purification of MOG from brain tissues, the extracellular domain of human MOG correspondin g to the N-terminal 121 amino acids was expressed in Escherichia coli as a glutathione sulfotransferase fusion protein. The expressed protei n was localized to inclusion bodies, and varying the growth parameters resulted in the solubilization of small amounts of GST-MOG that could be affinity purified on glutathione agarose columns. The fusion prote in found in the inclusion bodies could be solubilized with urea. The s olubilized fusion protein was cleaved with thrombin, and the extracell ular domain was purified by CM Sephadex 50 chromatography to homogenei ty. Injection of recombinant human MOG into different strains of mice resulted in the induction of an MS-like disease, characterized by seve re neurological impairment and extensive CNS demyelinated lesions. Rec ombinant MOG produced in E. coli should prove to be useful as a highly purified biological reagent for immunological, pathological, function al, and structural studies.