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http://purl.uniprot.org/citations/23449721http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/23449721http://www.w3.org/2000/01/rdf-schema#comment"

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."xsd:string
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http://purl.uniprot.org/citations/23449721http://purl.uniprot.org/core/author"Hu J."xsd:string
http://purl.uniprot.org/citations/23449721http://purl.uniprot.org/core/author"Meng H."xsd:string
http://purl.uniprot.org/citations/23449721http://purl.uniprot.org/core/author"Qian J."xsd:string
http://purl.uniprot.org/citations/23449721http://purl.uniprot.org/core/author"Hao H."xsd:string
http://purl.uniprot.org/citations/23449721http://purl.uniprot.org/core/author"Eberhart C.G."xsd:string
http://purl.uniprot.org/citations/23449721http://purl.uniprot.org/core/author"Jun A.S."xsd:string
http://purl.uniprot.org/citations/23449721http://purl.uniprot.org/core/author"Lackner E.M."xsd:string
http://purl.uniprot.org/citations/23449721http://purl.uniprot.org/core/author"Matthaei M."xsd:string
http://purl.uniprot.org/citations/23449721http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/23449721http://purl.uniprot.org/core/name"Invest Ophthalmol Vis Sci"xsd:string
http://purl.uniprot.org/citations/23449721http://purl.uniprot.org/core/pages"1931-1940"xsd:string
http://purl.uniprot.org/citations/23449721http://purl.uniprot.org/core/title"Endothelial cell whole genome expression analysis in a mouse model of early-onset Fuchs' endothelial corneal dystrophy."xsd:string
http://purl.uniprot.org/citations/23449721http://purl.uniprot.org/core/volume"54"xsd:string
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