Complex alternative splicing of the myelin oligodendrocyte glycoprotein gene is unique to human and non‐human primates

• Published in: Journal of neurochemistry Vol. 98; no. 6; pp. 1707 - 1717
• Main Authors: Delarasse, Cécile, Della Gaspera, Bruno, Lu, Chuan Wei, Lachapelle, François, Gelot, Antoinette, Rodriguez, Diana, Dautigny, André, Genain, Claude, Pham‐Dinh, Danielle
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.09.2006; Blackwell; Wiley
• Subjects: Alternative Splicing; Amino Acid Sequence; Animals; Biochemistry; Biological and medical sciences; Brain; Callithrix; Cattle; Central Nervous System - embryology; Cerebrospinal fluid. Meninges. Spinal cord; Child, Preschool; evolution; experimental autoimmune encephalomyelitis; Fetus - metabolism; Gene expression; Genes; Genetic diversity; Glycoproteins; Humans; Infant; Life Sciences; Macaca fascicularis; Medical sciences; Mice; Mice, Inbred C57BL; Molecular Sequence Data; multiple sclerosis; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; myelin; Myelin Proteins; Myelin-Associated Glycoprotein - genetics; Myelin-Associated Glycoprotein - metabolism; Myelin-Oligodendrocyte Glycoprotein; Nervous system (semeiology, syndromes); Neurobiology; Neurology; Neurons and Cognition; Primates; Primates - genetics; RNA, Messenger - genetics; Rodents; Autoimmunity; Alternative splicing; Membrane protein; myelin/oligodendrocyte glycoprotein; Neuroglia; Central nervous system; Inflammatory disease; experimental autoimmune encephalomyelitis; Gene; Oligodendrocyte; Primates; Human; Immunopathology; Nervous system diseases; Immune response; Myelin; multiple sclerosis; Rodentia; Glycoprotein; evolution; Gene expression; Cerebral disorder; Vertebrata; Mammalia; Mouse; Central nervous system disease; Spinal cord disease
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2006.04053.x

Myelin/oligodendrocyte glycoprotein (MOG) is a minor integral membrane protein specific to CNS myelin, encoded by a gene located in the major histocompatibility complex. MOG is an highly encephalitogenic autoantigen and a target for autoaggressive immune responses in CNS inflammatory demyelinating diseases. We performed transcriptomic analyses for a gene expressed only in mammalian CNS, myelin oligodendrocyte glycoprotein (MOG). Complex splicing patterns were exclusively found in primates and not in mice, unlike patterns found for other myelin protein genes. In addition to those shared with rodents, these multiple MOG isoforms likely support functions unique to the primate order, in particular maintenance of myelin structure, intracellular signaling, and modulation of CNS autoimmunity via exposure of specific MOG determinants. Developmentally, in human brain the splice variants of MOG appear at a late stage compared to the major isoform, coincidental with myelination and myelin maturation, unlike other myelin proteins. These findings are discussed within the framework of a biological basis for phenotype diversity in recent mammalian evolution and for the notoriously variable clinical expression of diseases such as multiple sclerosis.