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  Progressive axonopathy when oligodendrocytes lack the myelin protein CMTM5

Buscham, T. J., Eichel-Vogel, M. A., Steyer, A. M., Jahn, O., Strenzke, N., Dardawal, R., et al. (2022). Progressive axonopathy when oligodendrocytes lack the myelin protein CMTM5. eLife, 11: e75523. doi:10.7554/eLife.75523.

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Buscham, T. J.1, Author           
Eichel-Vogel, M. A., Author
Steyer, A. M.1, Author           
Jahn, O.2, Author           
Strenzke, N., Author
Dardawal, R., Author
Memhave, T. R., Author
Siems, S. B.1, Author           
Müller, C., Author
Meschkat, M.1, Author           
Sun, T.1, Author           
Ruhwedel, T.1, Author           
Möbius, W.1, Author           
Krämer-Albers, E.-M., Author
Boretius, S., Author
Nave, K.-A.1, Author           
Werner, H. B.1, Author           
Affiliations:
1Department of Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society, ou_3350301              
2Department of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society, ou_3350300              

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 Abstract: Oligodendrocytes facilitate rapid impulse propagation along the axons they myelinate and support their long-term integrity. However, the functional relevance of many myelin proteins has remained unknown. Here, we find that expression of the tetraspan-transmembrane protein CMTM5 (chemokine-like factor-like MARVEL-transmembrane domain containing protein 5) is highly enriched in oligodendrocytes and central nervous system (CNS) myelin. Genetic disruption of the Cmtm5 gene in oligodendrocytes of mice does not impair the development or ultrastructure of CNS myelin. However, oligodendroglial Cmtm5 deficiency causes an early-onset progressive axonopathy, which we also observe in global and tamoxifen-induced oligodendroglial Cmtm5 mutants. Presence of the WldS mutation ameliorates the axonopathy, implying a Wallerian degeneration-like pathomechanism. These results indicate that CMTM5 is involved in the function of oligodendrocytes to maintain axonal integrity rather than myelin biogenesis.

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Language(s): eng - English
 Dates: 2022-03-11
 Publication Status: Published online
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 Rev. Type: Peer
 Identifiers: DOI: 10.7554/eLife.75523
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Title: eLife
Source Genre: Journal
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Pages: - Volume / Issue: 11 Sequence Number: e75523 Start / End Page: - Identifier: -