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A Drug-Inducible Transgenic Zebrafish Model for Myelinating Glial Cell Ablation

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Oligodendrocytes

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1936))

Abstract

To study cellular and molecular mechanisms of demyelination and remyelination in vivo, we developed a transgenic zebrafish line, Tg(mbp:mCherry-NTR), in which expression of the bacterial enzyme nitroreductase (NTR) is driven under the myelin basic protein promoter (mbp) and thus is expressed in myelinating glia. When NTR-expressing larvae are treated with the prodrug metronidazole, the reaction between NTR and Mtz results in a toxic metabolite which selectively kills NTR-expressing cells. Using the Tg(mbp:mCherry-NTR) line, we can ablate two-thirds of oligodendrocytes following a 2-day MTZ treatment. Demyelination is evident seven days later, and remyelination is observed 16 days after Mtz treatment. The Tg(mbp:mCherry-NTR) model can be used to image cell behavior during, and to test how genetic manipulations or chemical compounds regulate, demyelination and remyelination. In this chapter, we describe the methods we used to characterize the oligodendrocyte loss, demyelination and remyelination in the Tg(mbp:mCherry-NTR) model.

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Authors and Affiliations

  1. Centre for Discovery Brain Sciences, The University of Edinburgh, Edinburgh, UK

    Marja J. Karttunen & David A. Lyons

Authors
  1. Marja J. Karttunen
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  2. David A. Lyons
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Corresponding author

Correspondence to David A. Lyons .

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Editors and Affiliations

  1. Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK

    David A. Lyons

  2. Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK

    Linde Kegel

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Karttunen, M.J., Lyons, D.A. (2019). A Drug-Inducible Transgenic Zebrafish Model for Myelinating Glial Cell Ablation. In: Lyons, D., Kegel, L. (eds) Oligodendrocytes. Methods in Molecular Biology, vol 1936. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-9072-6_13

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  • DOI: https://doi.org/10.1007/978-1-4939-9072-6_13

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-9070-2

  • Online ISBN: 978-1-4939-9072-6

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