Jacobs, Erin C. and Pribyl, Thomas M. and Feng, Ji-Ming and Kampf, Kathy and Spreur, Vilma and Campagnoni, Celia and Colwell, Christopher S. and Reyes, Samuel D. and Martin, Melanie and Handley, Vance and Hiltner, Timothy D. and Readhead, Carol and Jacobs, Russell E. and Messing, Albee and Fisher, Robin S. and Campagnoni, Anthony T. (2005) Region-Specific Myelin Pathology in Mice Lacking the Golli Products of the Myelin Basic Protein Gene. Journal of Neuroscience, 25 (30). pp. 7004-7013. ISSN 0270-6474. PMCID PMC6724835. doi:10.1523/JNEUROSCI.0288-05.2005. https://resolver.caltech.edu/CaltechAUTHORS:20160212-081324330
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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 Ca^(2+) transients in purified cortical oligodendrocytes studied in vitro. The Ca^(2+) 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.
Item Type: | Article | ||||||||||||
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Additional Information: | © 2005 Society for Neuroscience. For the first six months after publication SfN’s license will be exclusive. Beginning six months after publication the Work will be made freely available to the public on SfN’s website to copy, distribute, or display under a Creative Commons Attribution 4.0 International (CC BY 4.0) license (https://creativecommons.org/licenses/by/4.0/). Received Jan. 20, 2005; revised June 7, 2005; accepted June 9, 2005. This work was supported by National Institutes of Health Grant NS23022 and National Multiple Sclerosis Society Grant RG2693 to A.T.C. We thank Birgitta Sjostrand and the University of California Los Angeles Brain Research Institute Electron Microscopic Core for specimen preparation and use of microscopic facilities. | ||||||||||||
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Subject Keywords: | oligodendrocytes; calcium imaging; dysmyelination; visual cortex; optic nerve; ablation | ||||||||||||
Issue or Number: | 30 | ||||||||||||
PubMed Central ID: | PMC6724835 | ||||||||||||
DOI: | 10.1523/JNEUROSCI.0288-05.2005 | ||||||||||||
Record Number: | CaltechAUTHORS:20160212-081324330 | ||||||||||||
Persistent URL: | https://resolver.caltech.edu/CaltechAUTHORS:20160212-081324330 | ||||||||||||
Official Citation: | Region-Specific Myelin Pathology in Mice Lacking the Golli Products of the Myelin Basic Protein Gene Erin C. Jacobs, Thomas M. Pribyl, Kathy Kampf, Celia Campagnoni, Christopher S. Colwell, Samuel D. Reyes, Melanie Martin, Vance Handley, Timothy D. Hiltner, Carol Readhead, Russell E. Jacobs, Albee Messing, Robin S. Fisher, and Anthony T. Campagnoni The Journal of Neuroscience, 27 July 2005, 25(30):7004-7013; doi:10.1523/JNEUROSCI.0288-05.2005 | ||||||||||||
Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | ||||||||||||
ID Code: | 64449 | ||||||||||||
Collection: | CaltechAUTHORS | ||||||||||||
Deposited By: | Ruth Sustaita | ||||||||||||
Deposited On: | 19 Feb 2016 22:01 | ||||||||||||
Last Modified: | 10 Nov 2021 23:31 |
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