Generation of demyelination models by targeted ablation of oligodendrocytes in the zebrafish CNS

Ah Young Chung, Pan Soo Kim, Suhyun Kim, Eunmi Kim, Dohyun Kim, Inyoung Jeong, Hwan Ki Kim, Jae Ho Ryu, Cheol Hee Kim, June Choi, Jin Ho Seo, Hae Chul Park

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Demyelination is the pathological process by which myelin sheaths are lost from around axons, and is usually caused by a direct insult targeted at the oligodendrocytes in the vertebrate central nervous system (CNS). A demyelinated CNS is usually remyelinated by a population of oligodendrocyte progenitor cells, which are widely distributed throughout the adult CNS. However, myelin disruption and remyelination failure affect the normal function of the nervous system, causing human diseases such as multiple sclerosis. In spite of numerous studies aimed at understanding the remyelination process, many questions still remain unanswered. Therefore, to study remyelination mechanisms in vivo, a demyelination animal model was generated using a transgenic zebrafish system in which oligodendrocytes are conditionally ablated in the larval and adult CNS. In this transgenic system, bacterial nitroreductase enzyme (NTR), which converts the prodrug metronidazole (Mtz) into a cytotoxic DNA cross-linking agent, is expressed in oligodendrocyte lineage cells under the control of the mbp and sox10 promoter. Exposure of transgenic zebrafish to Mtz-containing media resulted in rapid ablation of oligodendrocytes and CNS demyelination within 48 h, but removal of Mtz medium led to efficient remyelination of the demyelinated CNS within 7 days. In addition, the demyelination and remyelination processes could be easily observed in living transgenic zebrafish by detecting the fluorescent protein, mCherry, indicating that this transgenic system can be used as a valuable animal model to study the remyelination process in vivo, and to conduct high-throughput primary screens for new drugs that facilitate remyelination.

Original languageEnglish
Pages (from-to)82-87
Number of pages6
JournalMolecules and Cells
Volume36
Issue number1
DOIs
Publication statusPublished - 2013 Jul 1

Fingerprint

Oligodendroglia
Demyelinating Diseases
Zebrafish
Central Nervous System
Metronidazole
Myelin Sheath
Animal Models
Nitroreductases
Prodrugs
Pathologic Processes
Nervous System
Multiple Sclerosis
Axons
Vertebrates
Stem Cells
DNA
Enzymes
Pharmaceutical Preparations
Population

Keywords

  • Cns
  • Demyelination
  • Nfsb
  • Oligodendrocyte
  • Zebrafish

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Generation of demyelination models by targeted ablation of oligodendrocytes in the zebrafish CNS. / Chung, Ah Young; Kim, Pan Soo; Kim, Suhyun; Kim, Eunmi; Kim, Dohyun; Jeong, Inyoung; Kim, Hwan Ki; Ryu, Jae Ho; Kim, Cheol Hee; Choi, June; Seo, Jin Ho; Park, Hae Chul.

In: Molecules and Cells, Vol. 36, No. 1, 01.07.2013, p. 82-87.

Research output: Contribution to journalArticle

Chung, AY, Kim, PS, Kim, S, Kim, E, Kim, D, Jeong, I, Kim, HK, Ryu, JH, Kim, CH, Choi, J, Seo, JH & Park, HC 2013, 'Generation of demyelination models by targeted ablation of oligodendrocytes in the zebrafish CNS', Molecules and Cells, vol. 36, no. 1, pp. 82-87. https://doi.org/10.1007/s10059-013-0087-9
Chung, Ah Young ; Kim, Pan Soo ; Kim, Suhyun ; Kim, Eunmi ; Kim, Dohyun ; Jeong, Inyoung ; Kim, Hwan Ki ; Ryu, Jae Ho ; Kim, Cheol Hee ; Choi, June ; Seo, Jin Ho ; Park, Hae Chul. / Generation of demyelination models by targeted ablation of oligodendrocytes in the zebrafish CNS. In: Molecules and Cells. 2013 ; Vol. 36, No. 1. pp. 82-87.
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