Gene array analysis comparison between rat collagen-induced arthritis and human rheumatoid arthritis
Scandinavian Journal of Immunology
|May 20, 2008
Summary
The rat collagen-induced arthritis (CIA) model shows significant differences in gene expression compared to human rheumatoid arthritis (RA). This comprehensive gene analysis highlights distinct inflammatory pathways, questioning CIA
Area of Science:
- Immunology and Rheumatology
- Genomics and Bioinformatics
Background:
- Collagen-induced arthritis (CIA) is a widely used animal model for studying rheumatoid arthritis (RA).
- Comprehensive gene expression analysis is crucial for understanding disease mechanisms and validating animal models.
Purpose of the Study:
- To conduct the first comprehensive gene expression analysis of rat CIA.
- To compare gene expression profiles of rat CIA and human RA to evaluate model relevance.
- To identify differences and similarities in inflammatory pathways between rat CIA and human RA.
Main Methods:
- Genome-wide gene expression analysis using Affymetrix arrays for both rat CIA and human RA samples.
- Comparative analysis of highly induced genes, immunological-associated genes, and pathway analysis (Ingenuity Pathway Analysis - IPA).
Main Results:
- Human RA showed upregulation of B-cell-associated genes (immunoglobulins, CD20, TNFSF13b/BLyS, CXCL13).
- Rat CIA exhibited upregulation of genes primarily expressed in macrophages and dendritic cells.
- Only three out of 22 significant pathways (IL6, chemokine signaling, antigen presentation) overlapped between human RA and rat CIA.
Conclusions:
- Significant differences exist in inflammatory mechanisms between human RA and rat CIA.
- Genome-wide comparative gene expression analysis is valuable for assessing the translational relevance of animal models.
- The rat CIA model may not fully recapitulate the molecular pathology of human RA, particularly concerning B-cell involvement.
Related Concept Videos
01:11Genome-wide Association Studies-GWAS
Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
GWAS does not require the identification of the target gene involved in...
01:20The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...