title: Complex alternative splicing of the myelin oligodendrocyte glycoprotein gene is unique to human and non-human primates.
abstract: 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.
authors.affiliation: INSERM UMR 546, Paris, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Delarasse
authors.forename: Bruno
authors.initials: B
authors.lastname: Della Gaspera
authors.forename: Chuan Wei
authors.initials: CW
authors.lastname: Lu
authors.forename: François
authors.initials: F
authors.lastname: Lachapelle
authors.forename: Antoinette
authors.initials: A
authors.lastname: Gelot
authors.forename: Diana
authors.initials: D
authors.lastname: Rodriguez
authors.forename: André
authors.initials: A
authors.lastname: Dautigny
authors.forename: Claude
authors.initials: C
authors.lastname: Genain
authors.forename: Danielle
authors.initials: D
authors.lastname: Pham-Dinh
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D002144:Callithrix; D002417:Cattle; D002490:Central Nervous System / Q000196:embryology; D002675:Child, Preschool; D005333:Fetus / Q000378:metabolism; D006801:Humans; D007223:Infant; D008252:Macaca fascicularis; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000235:genetics* / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein; D011323:Primates / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics
chemical_list: C571326:MOG protein, human; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D012333:RNA, Messenger