Myelin-oligodendrocyte glycoprotein (MOG) is a member of the immunoglobulin (Ig) superfamily, exclusively expressed in the central nervous system (CNS). MOG is an intrinsic membrane protein characterized by a N-terminal extracellular immunoglobulin Ig like variable (Ig-like V-type) domain, two hydrophobic transmembrane domains and a cytoplasmic C-terminal region. The N-terminal MOG domain has strong homology with the N-terminus of butyrophilin, a protein expressed in the lactating mammary gland. Human MOG gene is localized to chromosome 6p22-p21.3 (band C of mouse chromosome 17) at the distal end of the MHC class Ib region.
MOG contains nine exons and eight separating introns, giving rise to at least eight alternatively spliced variants encoding for the MOG-alpha1-4 and MOG-beta 1 to 4 isoforms (16 to 26 kDa). The different MOG isoforms may interact to form homo- and heterodimers and trimers (55 and 78 kDa). During the last step of myelinogenesis, MOG is expressed in the CNS on the outermost surface (external lamella) of mature myelin sheaths and on the cell surface of myelinating oligodendrocytes.
MOG has a variety of functions including a role as a cellular adhesion molecule. It may be involved also in the completion and/or maintenance of the myelin sheath and in cell-cell communication. MOG is also thought to function as a regulator of oligodendrocyte microtubule stability and as a mediator of interactions between myelin and the immune system in the complement cascade. Although MOG is a relatively minor component of the myelin membrane, it is a primary
auto-antigen target involved in the pathogenesis of immune-mediated demyelinating diseases including experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis.
The MOG 35-55 peptide is an immunodominant epitope of MOG that induces strong T and B cell responses. A single injection of this peptide fragment can produce an exacerbating-remitting neurologic disease with extensive plaque-like demyelination, which may serve as a model for investigating multiple sclerosis.
