PUBLICATION
Zebrafish model of human Zellweger syndrome reveals organ-specific accumulation of distinct fatty acid species and widespread gene expression changes
- Authors
- Takashima, S., Takemoto, S., Toyoshi, K., Ohba, A., Shimozawa, N.
- ID
- ZDB-PUB-210522-2
- Date
- 2021
- Source
- Molecular genetics and metabolism 133(3): 307-323 (Journal)
- Registered Authors
- Keywords
- Fatty acid profile, Peroxisomes, Transcriptome, Zebrafish, Zellweger syndrome
- Datasets
- GEO:GSE172233
- MeSH Terms
-
- Animals
- Disease Models, Animal
- Fatty Acids/analysis
- Fatty Acids/classification
- Fatty Acids/metabolism*
- Female
- Gene Expression*
- Gene Expression Profiling
- Humans
- Liver/pathology
- Male
- Peroxins/genetics
- Peroxisomes/pathology*
- Zebrafish/genetics
- Zellweger Syndrome/genetics*
- Zellweger Syndrome/physiopathology*
- PubMed
- 34016526 Full text @ Mol. Genet. Metab.
Citation
Takashima, S., Takemoto, S., Toyoshi, K., Ohba, A., Shimozawa, N. (2021) Zebrafish model of human Zellweger syndrome reveals organ-specific accumulation of distinct fatty acid species and widespread gene expression changes. Molecular genetics and metabolism. 133(3):307-323.
Abstract
In Zellweger syndrome (ZS), lack of peroxisome function causes physiological and developmental abnormalities in many organs such as the brain, liver, muscles, and kidneys, but little is known about the exact pathogenic mechanism. By disrupting the zebrafish pex2 gene, we established a disease model for ZS and found that it exhibits pathological features and metabolic changes similar to those observed in human patients. By comprehensive analysis of the fatty acid profile, we found organ-specific accumulation and reduction of distinct fatty acid species, such as an accumulation of ultra-very-long-chain polyunsaturated fatty acids (ultra-VLC-PUFAs) in the brains of pex2 mutant fish. Transcriptome analysis using microarray also revealed mutant-specific gene expression changes that might lead to the symptoms, including reduction of crystallin, troponin, parvalbumin, and fatty acid metabolic genes. Our data indicated that the loss of peroxisomes results in widespread metabolic and gene expression changes beyond the causative peroxisomal function. These results suggest the genetic and metabolic basis of the pathology of this devastating human disease.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping