COMPOSITIONS AND METHODS COMPRISING COMPLEX ALTERNATIVE SPLICE VARIANTS OF MYELIN/OLIGODENDROCYTE GENES (MOGS) AND ANTIBODIES DIRECTED THERETO

摘要

Provided are isolated MOG isoforms generated in vivo by exon splicing and that contribute to phenotypic diversity in the peripheral and central nervous systems. Presented herein are transcriptomic analyses for a gene expressed only in mammalian nervous system, myelin oligodendrocyte glycoprotein (MOG). Complex splicing patterns were exclusively found in primates and not in mice. Primate-specific transcripts predicted the existence of multiple MOG isoforms including truncated intra-membranous and/or alternate cytoplasmic domains, and soluble secreted proteins with AIu motifs. The multitude of MOG isoforms is predictive of functions unique to primates, including humans, with regards to maintenance of myelin structure, intracellular signaling, and/or expression of CNS autoimmunity via exposure of specific epitope determinants. Differential expression of MOG isoforms along the neuroaxis is correlative of the broad variability of phenotypes that characteristic of the CNS demyelinating disorder multiple sclerosis. MOG splice variants, isoforms, antibodies, and methods presented herein may be suitably employed for the identification, characterization, and treatment of diseases including, but not limited to, demyelinating and other neurodegenerative, infectious, inflammatory, inherited, and metabolic disorders such as multiple sclerosis (MS) and Alexander's disease.