REGULATION OF MYELIN OLIGODENDROCYTE GLYCOPROTEIN IN DIFFERENT SPECIES THROUGHOUT DEVELOPMENT

The assembly and function of central nervous system (CNS) myelin requi res the coordinated expression of several myelin-specific proteins, in cluding myelin oligodendrocyte glycoprotein (MOG). Despite the recent cloning of MOG, the function of this molecule is still unknown. Becaus e MOG is a late marker of oligodendrocyte maturation and is exclusivel y expressed in the CNS on the outermost lamellae of the myelin membran e, it is possible that this molecule plays an important role in the co ntrol and maintenance of myelination. Furthermore, as a member of the immunoglobulin superfamily that carries the L2/HNK-1 epitope, it has a lso been suggested that MOG is involved in cell-cell interaction, perh aps functioning as an adhesive molecule for bundles of nerve fibres. I n order to further delineate the role of MOG throughout development we have analysed, by immunoblotting, the developmental appearance and ac cumulation pattern of MOG in the CNS of three mammalian species. We ha ve also purified MOG to homogeneity from five different species includ ing rat, guinea pig, bovine, monkey and human. Immunoblotting revealed two major MOG bands at 28 and 55 kD in all species. The 55 kD band ap pears to be a dimer of the lower band although treatment with 2-mercap toethanol or EDTA failed to abolish it. Purified MOG from all species also displayed faint reactivity with bands at 36, 48 and 78 kD. While the 78 kD band may represent a trimer of MOG, the identity of the othe r bands remains unknown. Developmental studies in mouse, rat, guinea p ig and bovine showed that as for other myelin proteins, MOG displayed a caudorostral gradient of expression, appearing in the spinal cord be fore the brain. The sensitivity of the detection system used here allo wed us to detect MOG protein earlier than in previous reports such tha t its presence was clearly demonstrated in the CNS of mice and rats at 14 and 10 days after birth, respectively. Analysis of MOG expression in a novel transgenic mouse model that has both delayed and reduced my elination revealed that, like other myelin proteins, MOG expression wa s delayed compared with normal littermates. These results demonstrate that the expression of MOG is similar in all species and is regulated in a manner consistent with other myelin-specific proteins.