Endothelial cell whole genome expression analysis in a mouse model of early-onset Fuchs' endothelial corneal dystrophy
Standard
Endothelial cell whole genome expression analysis in a mouse model of early-onset Fuchs' endothelial corneal dystrophy. / Matthaei, Mario; Hu, Jianfei; Meng, Huan; Lackner, Eva-Maria; Eberhart, Charles G; Qian, Jiang; Hao, Haiping; Jun, Albert S.
In: INVEST OPHTH VIS SCI, Vol. 54, No. 3, 01.03.2013, p. 1931-40.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Endothelial cell whole genome expression analysis in a mouse model of early-onset Fuchs' endothelial corneal dystrophy
AU - Matthaei, Mario
AU - Hu, Jianfei
AU - Meng, Huan
AU - Lackner, Eva-Maria
AU - Eberhart, Charles G
AU - Qian, Jiang
AU - Hao, Haiping
AU - Jun, Albert S
PY - 2013/3/1
Y1 - 2013/3/1
N2 - 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.
AB - 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.
KW - Aged
KW - Animals
KW - Cyclooxygenase 2
KW - Disease Models, Animal
KW - Endothelium, Corneal
KW - Female
KW - Fuchs' Endothelial Dystrophy
KW - Genes, jun
KW - Genome
KW - Genome-Wide Association Study
KW - Humans
KW - Male
KW - Mice
KW - Mice, Knockout
KW - Microscopy, Confocal
KW - Phenotype
KW - RNA, Messenger
KW - Real-Time Polymerase Chain Reaction
KW - Up-Regulation
U2 - 10.1167/iovs.12-10898
DO - 10.1167/iovs.12-10898
M3 - SCORING: Journal article
C2 - 23449721
VL - 54
SP - 1931
EP - 1940
JO - INVEST OPHTH VIS SCI
JF - INVEST OPHTH VIS SCI
SN - 0146-0404
IS - 3
ER -