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Updated: May 28, 2026
Cell Type-specific Gene Expression Profiling in the Mouse Liver
Published on: September 17, 2019
Identification of high-copper-responsive target pathways in Atp7b knockout mouse liver by GSEA on microarray data
Kan He1, Zhenliang Chen, Yufang Ma
1School of Agriculture and Biology, Department of Animal Sciences, Shanghai Jiao Tong University, Shanghai, Peoples' Republic of China. hekan@sjtu.edu.cn
Abstract:
The mutation of the Wilson's disease protein ATP7B has been widely used to study the direct link between hepatic high copper and development of liver pathology. Several studies have used gene expression profiling of high-copper effects to identify the key genes in the process, but few focused on the involved pathways and the coexpression patterns of associated pathways. We used a microarray data set from the public database library of GEO (Gene Expression Omnibus), which is associated with liver transcriptome in the early stages of copper accumulation in the mouse model of Wilson's disease under Atp7b knockout. To be more powerful than conventional single-gene methods in the study of complex diseases, we applied gene set enrichment analysis (GSEA) on the data sets and performed candidate transcription factors selection. As a result, 16 upregulated pathways such as tryptophan metabolism and cell cycle and 15 downregulated pathways such as TCA cycle and PPAR signaling pathway were identified as high-copper-responsive target pathways in Atp7b knockout mouse liver, and most of them had not been reported on previously. Finally, coexpression networks of related pathways were constructed with the significant core genes and transcription factors such as SREBP1 and PPARG. The results of our study may help us better understand the molecular mechanisms of high-copper effects in mice liver in genome-wide.
Insights
Wilson's disease protein ATP7B mutations cause high hepatic copper accumulation. This study identified novel high-copper-responsive pathways and coexpression networks in mouse liver, advancing understanding of Wilson's disease pathology.
Area of Science:
- Genomics
- Molecular Biology
- Hepatology
Background:
- Wilson's disease is linked to ATP7B mutations and hepatic copper accumulation.
- Previous studies identified key genes but lacked focus on pathway involvement and coexpression patterns.
Purpose of the Study:
- To investigate high-copper-responsive pathways and coexpression networks in the early stages of Wilson's disease.
- To identify candidate transcription factors involved in copper accumulation-induced liver pathology.
Main Methods:
- Utilized microarray data from an Atp7b knockout mouse model of Wilson's disease.
- Applied Gene Set Enrichment Analysis (GSEA) to identify affected pathways.
- Constructed coexpression networks using significant core genes and transcription factors.
Main Results:
- Identified 16 upregulated pathways (e.g., tryptophan metabolism, cell cycle) and 15 downregulated pathways (e.g., TCA cycle, PPAR signaling).
- Most identified pathways were previously unreported in the context of high copper.
- Constructed coexpression networks highlighting key transcription factors like SREBP1 and PPARG.
Conclusions:
- This study provides a genome-wide understanding of molecular mechanisms underlying high copper effects in mouse liver.
- Findings offer insights into the pathogenesis of Wilson's disease and potential therapeutic targets.