Alternative isoforms of myelin/oligodendrocyte glycoprotein with variable cytoplasmic domains are expressed in human brain

The human myelin/oligodendrocyte glycoprotein (MOG) gene is encoded by 10 exons that exhibit a complex pattern of alternative splicing. This report demonstrates that several MOG-specific alternative splice variants are indeed expressed in human oligodendrocytes (OLs) and myelin during perinatal development and are retained through adulthood. While all forms possess the common extracellular Ig-like domain, these alternative MOG structures differ significantly in their respective cytoplasmic domains. Peptide-specific antibodies were generated to facilitate detection of these different MOG moieties. The fidelity of these antibodies is shown using N20 OLs expressing individual MOG variants. These antibodies also only co-localize with another well-characterized marker of OLs and myelin--PLP/DM20 proteins. Among the human tissue samples tested, very limited expression occurred by 36 weeks gestation for 2-3 MOG variants, and the remaining MOG isoforms were not evident until shortly after birth. This study represents the first evidence of alternative translation products from the MOG gene. To date, it is believed that alternative splicing of MOG is limited to primates. Recent completion of various genome projects has revealed that alternative splicing is much more prevalent than originally estimated, and species-specific alternative splicing is now being shown to be highly relevant to expanding proteomic diversity.