title: Endothelial cell whole genome expression analysis in a mouse model of early-onset Fuchs' endothelial corneal dystrophy.
abstract: OBJECTIVE
  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.
authors: Wilmer Eye Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA.
authors: Mario
authors: M
authors: Matthaei
authors: Jianfei
authors: J
authors: Hu
authors: Huan
authors: H
authors: Meng
authors: Eva-Maria
authors: EM
authors: Lackner
authors: Charles G
authors: CG
authors: Eberhart
authors: Jiang
authors: J
authors: Qian
authors: Haiping
authors: H
authors: Hao
authors: Albert S
authors: AS
authors: Jun
mesh_terms: D000368:Aged; D000818:Animals; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics*; D004195:Disease Models, Animal; D004728:Endothelium, Corneal / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005642:Fuchs' Endothelial Dystrophy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016758:Genes, jun / Q000235:genetics*; D016678:Genome / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human