title: Conditional knockout of TOG results in CNS hypomyelination.
abstract: The tumor overexpressed gene (TOG) protein is present in RNA granules that transport myelin basic protein (MBP) mRNA in oligodendrocyte processes to the myelin compartment. Its role was investigated by conditionally knocking it out (KO) in myelinating glia in vivo. TOG KO mice have severe motor deficits that are already apparent at the time of weaning. This phenotype correlates with a paucity of myelin in several CNS regions, the most severe being in the spinal cord. In the TOG KO optic nerve <30% of axons are myelinated. The number of oligodendrocytes in the corpus callosum, cerebellum, and cervical spinal cord is normal. In the absence of TOG, the most patent biochemical change is a large reduction in MBP content, yet normal amounts of MBP transcripts are found in the brain of affected animals. MBP transcripts are largely confined to the cell body of the oligodendrocytes in the TOG KO in contrast to the situation in wild type mice where they are found in the processes of the oligodendrocytes and in the myelin compartment. These findings indicate that MBP gene expression involves a post-transcriptional TOG-dependent step. TOG may be necessary for MBP mRNA assembly into translation permissive granules, and/or for transport to preferred sites of translation. GLIA 2017;65:489-501.
authors.affiliation: Department of Neuroscience, University of Connecticut School of Medicine, Farmington, Connecticut.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Maggipinto
authors.affiliation: Department of Neuroscience, University of Connecticut School of Medicine, Farmington, Connecticut.
authors.forename: Joshay
authors.initials: J
authors.lastname: Ford
authors.affiliation: Department of Neuroscience, University of Connecticut School of Medicine, Farmington, Connecticut.
authors.forename: Kristine H
authors.initials: KH
authors.lastname: Le
authors.affiliation: Department of Neuroscience, University of Connecticut School of Medicine, Farmington, Connecticut.
authors.forename: Jessica W
authors.initials: JW
authors.lastname: Tutolo
authors.affiliation: Department of Neuroscience, University of Connecticut School of Medicine, Farmington, Connecticut.
authors.forename: Miki
authors.initials: M
authors.lastname: Furusho
authors.affiliation: Department of Neuroscience, University of Connecticut School of Medicine, Farmington, Connecticut.
authors.forename: John W
authors.initials: JW
authors.lastname: Wizeman
authors.affiliation: Department of Neuroscience, University of Connecticut School of Medicine, Farmington, Connecticut.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Bansal
authors.affiliation: Department of Neuroscience, University of Connecticut School of Medicine, Farmington, Connecticut.
authors.forename: Elisa
authors.initials: E
authors.lastname: Barbarese
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics*; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000172:deficiency* / Q000235:genetics; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D009043:Motor Activity / Q000235:genetics; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism; D009836:Oligodendroglia / Q000473:pathology* / Q000648:ultrastructure; D004856:Postural Balance / Q000235:genetics
chemical_list: C587430:CKAP5 protein, mouse; D008869:Microtubule-Associated Proteins; D009185:Myelin Proteins
keywords: MT-associated protein; RNA granule; mRNA localization; myelin basic protein