ZFIN ID: ZDB-PUB-190302-6
A Drug-Inducible Transgenic Zebrafish Model for Myelinating Glial Cell Ablation
Karttunen, M.J., Lyons, D.A.
Date: 2019
Source: Methods in molecular biology (Clifton, N.J.)   1936: 227-238 (Chapter)
Registered Authors: Karttunen, Marja, Lyons, David A.
Keywords: Demyelination, Drug-inducible, Live imaging, Transgenic line, Zebrafish
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Demyelinating Diseases/chemically induced*
  • Demyelinating Diseases/metabolism
  • Disease Models, Animal
  • Gene Expression Regulation, Developmental
  • Metronidazole/pharmacology*
  • Myelin Basic Protein/genetics
  • Neuroglia
  • Nitroreductases/genetics
  • Nitroreductases/metabolism*
  • Oligodendroglia/cytology*
  • Oligodendroglia/drug effects
  • Promoter Regions, Genetic
  • Remyelination/drug effects
  • Zebrafish/genetics
  • Zebrafish/growth & development*
PubMed: 30820902 Full text @ Meth. Mol. Biol.
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.