Induction of clusterin Expression by Neuronal Cell Death in Zebrafish

Jeong, Y.M., Jin, T.E., Choi, J.H., Lee, M.S., Kim, H.T., Hwang, K.S., Park, D.S., Oh, H.W., Choi, J.K., Korzh, V., Schachner, M., You, K.H., Kim, C.H.
Journal of genetics and genomics = Yi chuan xue bao   41: 583-9 (Journal)
Registered Authors
Kim, Cheol-Hee, Korzh, Vladimir, Schachner, Melitta
Clusterin, Neurodegeneration, Neuronal cell death, Zebrafish
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Cell Death
  • Central Nervous System/embryology
  • Central Nervous System/metabolism
  • Central Nervous System/pathology
  • Clusterin/genetics*
  • Clusterin/physiology
  • Gene Expression
  • Humans
  • Molecular Sequence Data
  • Nerve Degeneration/etiology*
  • Nerve Degeneration/genetics
  • Nerve Degeneration/metabolism
  • Nerve Degeneration/pathology
  • Neurons/metabolism
  • Neurons/pathology
  • Notochord/embryology
  • Notochord/metabolism
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/physiology
25434681 Full text @ J. Genet. Genomics
Clusterin, a protein associated with multiple functions, is expressed in a wide variety of mammalian tissues. Although clusterin is known to be involved in neurodegenerative diseases, ageing, and tumorigenesis, a detailed analysis of the consequences of gain- or loss-of-function approaches has yet to be performed to understand the underlying mechanisms of clusterin functions. Since clusterin levels change in neurological diseases, it is likely that clusterin contributes to cell death and degeneration in general. Zebrafish was investigated as a model system to study human diseases. During development, zebrafish clusterin was expressed in the notochord and nervous system. Embryonic overexpression of clusterin by mRNA microinjection did not affect axis formation, whereas its knock-down by anti-sense morpholino treatment resulted in neuronal cell death. To analyze the function of clusterin in neurodegeneration, a transgenic zebrafish was investigated, in which nitroreductase expression is regulated under the control of a neuron-specific huC promoter which is active between the stages of early neuronal precursors and mature neurons. Nitroreductase turns metronidazole into a cytotoxic agent that induces cell death within 12 h. After metronidazole treatment, transgenic zebrafish showed neuron-specific cell death. Interestingly, we also observed a dramatic induction of clusterin expression in the brain and spinal cord in these fish, suggesting a direct or indirect role of clusterin in neuronal cell death and thus, more generally, in neurodegeneration.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes