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Endothelial cell whole genome expression analysis in a mouse model of early-onset Fuchs' endothelial corneal dystrophy
- Source :
- Investigative ophthalmologyvisual science. 54(3)
- Publication Year :
- 2013
-
Abstract
- PURPOSE To investigate the endothelial gene expression profile in a Col8a2 Q455K mutant knock-in mouse model of early-onset Fuchs' endothelial corneal dystrophy (FECD) and identify potential targets that can be correlated to human late-onset FECD. METHODS Diseased or normal endothelial phenotypes were verified in 12-month-old homozygous Col8a2(Q455K/Q455K) mutant and wild-type mice by clinical confocal microscopy. An endothelial whole genome expression profile was generated by microarray-based analysis. Result validation was performed by real-time PCR. Endothelial COX2 and JUN expression was further studied in human late-onset FECD compared to normal samples. RESULTS Microarray analysis demonstrated endothelial expression of 24,538 genes (162 up-regulated and 172 down-regulated targets) and identified affected gene ontology terms including Response to Stress, Protein Metabolic Process, Protein Folding, Regulation of Apoptosis, and Transporter Activity. Real-time PCR assessment confirmed increased Cox2 (P = 0.001) and Jun mRNA (P = 0.03) levels in Col8a2(Q455K/Q455K) mutant compared to wild-type mice. In human FECD samples, real-time PCR demonstrated a statistically significant increase in COX2 mRNA (P < 0.0001) and JUN mRNA (P = 0.002) and tissue microarray analysis showed increased endothelial COX2 (P = 0.02) and JUN protein (P = 0.04). CONCLUSIONS The present study provides the first endothelial whole genome expression analysis in an animal model of FECD and represents a useful resource for future studies of the disease. In particular endothelial COX2 up-regulation warrants further investigation of its role in FECD.
- Subjects :
- Male
Endothelium
Fuchs Endothelial Dystrophy
Biology
Real-Time Polymerase Chain Reaction
Mice
Genes, jun
Gene expression
medicine
Animals
Humans
RNA, Messenger
Aged
Protein metabolic process
Mice, Knockout
Genome
Microscopy, Confocal
Microarray analysis techniques
Endothelium, Corneal
Fuchs' Endothelial Dystrophy
Articles
Molecular biology
Up-Regulation
Gene expression profiling
Endothelial stem cell
Disease Models, Animal
medicine.anatomical_structure
Real-time polymerase chain reaction
Phenotype
Cyclooxygenase 2
Female
Genome-Wide Association Study
Subjects
Details
- ISSN :
- 15525783
- Volume :
- 54
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Investigative ophthalmologyvisual science
- Accession number :
- edsair.doi.dedup.....d8b134b21ed28ed57b30931c64ecba88