title: Region-specific myelin pathology in mice lacking the golli products of the myelin basic protein gene.
abstract: The myelin basic protein (MBP) gene encodes two families of proteins, the classic MBP constituents of myelin and the golli-MBPs, the function of which is less well understood. In this study, targeted ablation of the golli-MBPs, but not the classic MBPs, resulted in a distinct phenotype unlike that of knock-outs (KOs) of the classic MBPs or other myelin proteins. Although the golli KO animals did not display an overt dysmyelinating phenotype, they did exhibit delayed and/or hypomyelination in selected areas of the brain, such as the visual cortex and the optic nerve, as determined by Northern and Western blots and immunohistochemical analysis with myelin protein markers. Hypomyelination in some areas, such as the visual cortex, persisted into adulthood. Ultrastructural analysis of the KOs confirmed both the delay and hypomyelination and revealed abnormalities in myelin structure and in some oligodendrocytes. Abnormal visual-evoked potentials indicated that the hypomyelination in the visual cortex had functional consequences in the golli KO brain. Evidence that the abnormal myelination in these animals was a consequence of intrinsic problems with the oligodendrocyte was indicated by an impaired ability of oligodendrocytes to form myelin sheets in culture and by the presence of abnormal Ca2+ transients in purified cortical oligodendrocytes studied in vitro. The Ca2+ results reported in this study complement previous results implicating golli proteins in modulating intracellular signaling in T-cells. Together, all these findings suggest a role for golli proteins in oligodendrocyte differentiation, migration, and/or myelin elaboration in the brain.
authors.affiliation: Neuropsychiatric Institute, University of California Los Angeles School of Medicine, Los Angeles, California 90024, USA.
authors.forename: Erin C
authors.initials: EC
authors.lastname: Jacobs
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Pribyl
authors.forename: Ji-Ming
authors.initials: JM
authors.lastname: Feng
authors.forename: Kathy
authors.initials: K
authors.lastname: Kampf
authors.forename: Vilma
authors.initials: V
authors.lastname: Spreur
authors.forename: Celia
authors.initials: C
authors.lastname: Campagnoni
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Colwell
authors.forename: Samuel D
authors.initials: SD
authors.lastname: Reyes
authors.forename: Melanie
authors.initials: M
authors.lastname: Martin
authors.forename: Vance
authors.initials: V
authors.lastname: Handley
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Hiltner
authors.forename: Carol
authors.initials: C
authors.lastname: Readhead
authors.forename: Russell E
authors.initials: RE
authors.lastname: Jacobs
authors.forename: Albee
authors.initials: A
authors.lastname: Messing
authors.forename: Robin S
authors.initials: RS
authors.lastname: Fisher
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Campagnoni
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D005260:Female; D006706:Homeostasis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D004676:Myelin Basic Protein; D009186:Myelin Sheath / Q000473:pathology*; D009413:Nerve Fibers, Myelinated / Q000473:pathology / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology*; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology*; D009900:Optic Nerve / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*; D014793:Visual Cortex / Q000473:pathology*
chemical_list: C499047:Mbp protein, mouse; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; D002118:Calcium