Dataset Information

Comparative proteome research in a zebrafish model for Vanishing White Matter disease

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). Although previous studies are being attempted to investigate the molecular mechanism of VWN by constructing variant models for each subunit of EIF2B that causes VWM disease. The underlying molecular mechanism of how mutations (MT) in EIF2B3 result in VWM is unknown. Based on our recently report, we constructed an eif2b3 knockout (eif2b3-/-) zebrafish (Danio rerio) model and performed quantitative proteomic analysis between the wide type (WT) and eif2b3-/- models to identify 25 differentially expressed proteins (DEPs). A total of 4 proteins were significantly up-regulated, and 21 proteins were significantly down-regulated in eif2b3-/- larvae compared to WT, respectively. Representatively, Lon protease and neutral amino acid transporter SLC1A4 were significantly increased in truncated eif2b3 zebrafish, and crystallin proteins were also significantly decreased. In conclusion, this study proposed the candidate proteins as a key regulator related to the progression of VWN disease through quantitative proteomic analysis in the first variant model of VWN disease.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Danio Rerio (zebrafish) (brachydanio Rerio)

TISSUE(S): Early Embryonic Cell

DISEASE(S): Leukoencephalopathy With Vanishing White Matter

SUBMITTER: Doeun Kim

LAB HEAD: Sangkyu Lee

PROVIDER: PXD023933 | Pride | 2021-09-10

REPOSITORIES: Pride

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Publications

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

Kim Doeun D Lee Yu-Ri YR Choi Tae-Ik TI Kim Se-Hee SH Kang Hoon-Chul HC Kim Cheol-Hee CH Lee Sangkyu S

International journal of molecular sciences 20210308 5

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 ...[more]

PMID: 33800130

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Project description:Three-month old zebrafish were fed Biodiet starter (4% body weight per day) with MeHg added at 0, 0.5, 5 and 50 ppm for six weeks. Atomic absorption spectrometry was applied to measure the level of MeHg in the whole fish body. Zebrafish at six weeks were sampled from each group for gene expression analysis by NimbleGen Gene Expression 12X135K zebrafish microarrays. MeHg-exposed trout and zebrafish did not show overt signs of toxicity, nor were significant differences seen in mortality, length, mass, or condition factor. The chronic accumulation of total Hg in zebrafish exhibited dose- and time-dependent patterns. The dysregulated genes in MeHg-treated fish have multiple functional annotations, such as involving metabolism, cellular development, ion binding, stress response, transcriptional regulation, and apoptotic pathways. These results show that numerous molecular pathways involved in the growth and development of multiple organ systems are disrupted by exposure to moderate levels of dietary MeHg. The dysregulated genes will be selected by further analysis and used as biomarkers for MeHg exposure in aquatic environments. This study will allow us to assess the potential impacts of low-level exposure to environmental MeHg in the food chain and on the health of humans and animals. Three-month old zebrafish (Danio rerio, average body 0.149 g) were fed Biodiet Starter (Bio-Oregon) 4% of body weight per day with MeHg added at 0ppm, 0.5ppm, 5ppm and 50ppm (with ethanol as vehicle). Fish at six weeks were sampled from each group for gene expression analysis. Three fish from each treatment group were used for microarray experiments. Total RNA from individual fish was isolated using Trizol reagent (Invitrogen) and further purified using the RNeasy MiniElute cleanup kit (Qiagen). Double-strand cDNA was synthesized from 10ug total RNA of individual fish by using Superscript Double-Stranded cDNA synthesis Kit (Invitrogen). ). One ug double strand DNA was labeled with Cy3 using One-Color DNA labeling Kit (NimbleGen), then hybridized to NimbleGen 12X135K array. The arrays were scanned at 2um on a NimbleGen MS200 scanner with auto-gain adjust. The TIFF images were gridded and extracted using NimbleScan v. 2.6. Expression data were normalized using the Robust Multichip Average (RMA) algorithm.

Dataset Information

Comparative proteome research in a zebrafish model for Vanishing White Matter disease

Publications

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

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