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.; Memhave, T. R.; Siems, S. B.; Müller, C.; Meschkat, M.; Sun, T.; Ruhwedel, T.; Möbius, W.; Krämer-Albers, E.-M.; Boretius, S.; Nave, K.-A.; Werner, H. B.

doi:10.1101/2021.11.22.469514

bioRxiv · 10.1101/2021.11.22.469514

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.·Memhave, T. R.·Siems, S. B.·Müller, C.·Meschkat, M.·Sun, T.·Ruhwedel, T.·Möbius, W.·Krämer-Albers, E.-M.·Boretius, S.·Nave, K.-A.·Werner, H. B.

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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 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 in 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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Buscham, T. J., Eichel-Vogel, M. A., Steyer, A. M., Jahn, O., Strenzke, N., Dardawal, R., Memhave, T. R., Siems, S. B., Müller, C., Meschkat, M., Sun, T., Ruhwedel, T., Möbius, W., Krämer-Albers, E.-M., Boretius, S., Nave, K.-A., Werner, H. B.. 2021-11-24. Progressive axonopathy when oligodendrocytes lack the myelin protein CMTM5. https://doi.org/10.1101/2021.11.22.469514

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