Targeted overexpression of a golli-myelin basic protein isoform to oligodendrocytes results in aberrant oligodendrocyte maturation and myelination
Authors: Vilma Spreuer
Erin C Jacobs
Anthony T Campagnoni
Samuel D Reyes
Celia W Campagnoni
Robin Fisher
Vance Handley
Kathy Kampf
M Irene Givogri
Wendy Macklin
Journal: ASN NEURO (2009)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: golli proteins; OL development; myelination; transgenic mouse; hypomyelination
Affiliations: Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA, Neuroscience Research Building, 635 Charles Young Drive, Los Angeles, CA 90095, USA., Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA, Neuroscience Research Building, 635 Charles Young Drive, Los Angeles, CA 90095, U.S.A., Department of Anatomy and Cell Biology, University of Illinois Chicago, 808 S. Wood Street #MC512, Chicago, IL 60612, U.S.A., Department of Cell and Developmental Biology, University of Colorado Medical School, Aurora, CO 80045, U.S.A.

Abstract:  Recently, several in vitro studies have shown that the golli-myelin basic proteins regulate Ca2+ homoeostasis in OPCs (oligodendrocyte precursor cells) and immature OLs (oligodendrocytes), and that a number of the functions of these cells are affected by cellular levels of the golli proteins. To determine the influence of golli in vivo on OL development and myelination, a transgenic mouse was generated in which the golli isoform J37 was overexpressed specifically within OLs and OPCs. The mouse, called JOE (J37-overexpressing), is severely hypomyelinated between birth and postnatal day 50. During this time, it exhibits severe intention tremors that gradually abate at later ages. After postnatal day 50, ultrastructural studies and Northern and Western blot analyses indicate that myelin accumulates in the brain, but never reaches normal levels. Several factors appear to underlie the extensive hypomyelination. In vitro and in vivo experiments indicate that golli overexpression causes a significant delay in OL maturation, with accumulation of significantly greater numbers of pre-myelinating OLs that fail to myelinate axons during the normal myelinating period. Immunohistochemical studies with cell death and myelin markers indicate that JOE OLs undergo a heightened and extended period of cell death and are unable to effectively myelinate until 2 months after birth. The results indicate that increased levels of golli in OPC/OLs delays myelination, causing significant cell death of OLs particularly in white matter tracts. The results provide in vivo evidence for a significant role of the golli proteins in the regulation of maturation of OLs and normal myelination. 

Retracted: No

PubPeer comments:
 image duplication ![file] Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. ,