PUBLICATION

Comparative Proteome Research in a Zebrafish Model for Vanishing White Matter Disease

Authors
Kim, D., Lee, Y.R., Choi, T.I., Kim, S.H., Kang, H.C., Kim, C.H., Lee, S.
ID
ZDB-PUB-210407-16
Date
2021
Source
International Journal of Molecular Sciences   22(5): (Journal)
Registered Authors
Kim, Cheol-Hee
Keywords
EIF2B, SLC1A4, Vanishing White Matter disease, comparative proteomics
MeSH Terms
  • Amino Acid Transport System ASC/genetics
  • Amino Acid Transport System ASC/metabolism*
  • Animals
  • Animals, Genetically Modified
  • Disease Models, Animal
  • Eukaryotic Initiation Factor-2B/deficiency
  • Eukaryotic Initiation Factor-2B/metabolism
  • Humans
  • Leukoencephalopathies/genetics
  • Leukoencephalopathies/metabolism*
  • Leukoencephalopathies/pathology
  • Proteome/genetics
  • Proteome/metabolism*
  • Proteomics
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
33800130 Full text @ Int. J. Mol. Sci.
Abstract
Vanishing white matter (VWM) disease is a genetic leukodystrophy leading to severe neurological disease and early death. VWM is caused by bi-allelic mutations in any of the five genes encoding the subunits of the eukaryotic translation factor 2B (EIF2B). Previous studies have attempted to investigate the molecular mechanism of VWN by constructing models for each subunit of EIF2B that causes VWM disease. The underlying molecular mechanisms of the way in which mutations in EIF2B3 result in VWM are largely unknown. Based on our recent results, we generated an eif2b3 knockout (eif2b3-/-) zebrafish model and performed quantitative proteomic analysis between the wild-type (WT) and eif2b3-/- zebrafish, and identified 25 differentially expressed proteins. Four proteins were significantly upregulated, and 21 proteins were significantly downregulated in eif2b3-/- zebrafish compared to WT. Lon protease and the neutral amino acid transporter SLC1A4 were significantly increased in eif2b3-/- zebrafish, and crystallin proteins were significantly decreased. The differential expression of proteins was confirmed by the evaluation of mRNA levels in eif2b3-/- zebrafish, using whole-mount in situ hybridization analysis. This study identified proteins which candidates as key regulators of the progression of VWN disease, using quantitative proteomic analysis in the first EIF2B3 animal model of VWN disease.
Genes / Markers
Figures
Figure Gallery
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes