Molecules and Cells

, Volume 36, Issue 1, pp 82–87 | Cite as

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
Article
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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.

Keywords

CNS demyelination nfsB oligodendrocyte zebrafish 
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Copyright information

© The Korean Society for Molecular and Cellular Biology and Springer Netherlands 2013

Authors and Affiliations

  • Ah-Young Chung
    • 1
  • Pan-Soo Kim
    • 2
  • Suhyun Kim
    • 1
  • Eunmi Kim
    • 1
  • Dohyun Kim
    • 1
  • Inyoung Jeong
    • 1
  • Hwan-Ki Kim
    • 1
  • Jae-Ho Ryu
    • 3
  • Cheol-Hee Kim
    • 4
  • June Choi
    • 5
  • Jin-Ho Seo
    • 6
  • Hae-Chul Park
    • 1
  1. 1.Graduate School of MedicineKorea UniversityAnsanKorea
  2. 2.Gyeonggi BiocenterGyeonggi Institute of Science and Technology Promotion (GSTEP)SuwonKorea
  3. 3.Genomic Design Bioengineering CompanyDaejeonKorea
  4. 4.Department of Biology and GRASTChungnam National UniversityDaejeonKorea
  5. 5.Department of Otorhinolaryngology-Head and Neck SurgeryKorea University School of MedicineSeoulKorea
  6. 6.Department of Agricultural Biotechnology and Center for Food and Bio ConvergenceSeoul National UniversitySeoulKorea

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