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Matthaei, M; Hu, J; Meng, H; Lackner, EM; Eberhart, CG; Qian, J; Hao, H; Jun, AS.
Endothelial cell whole genome expression analysis in a mouse model of early-onset Fuchs' endothelial corneal dystrophy.
Invest Ophthalmol Vis Sci. 2013; 54(3):1931-1940 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Lackner Eva-Maria
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Abstract:
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. 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. 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). 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.
Find related publications in this database (using NLM MeSH Indexing)
Aged -
Animals -
Cyclooxygenase 2 - biosynthesis
Disease Models, Animal -
Endothelium, Corneal - metabolism
Female -
Fuchs' Endothelial Dystrophy - genetics
Genes, jun - genetics
Genome - genetics
Genome-Wide Association Study - methods
Humans -
Male -
Mice -
Mice, Knockout -
Microscopy, Confocal -
Phenotype -
RNA, Messenger - genetics
Real-Time Polymerase Chain Reaction -
Up-Regulation -

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