title: Retinal disease in mice lacking hypoxia-inducible transcription factor-2alpha.
abstract: OBJECTIVE
  To characterize ocular disease in HIF-2alpha-null mice.
  
  
  METHODS
  Histologic, electroretinographic (ERG), and molecular studies were performed on samples obtained from age- and gender-matched HIF-2alpha-null (HIF-2alpha-KO), HIF-2alpha-heterozygous (HIF-2alpha-HET), and wild-type (WT) littermate mice.
  
  
  RESULTS
  HIF-2alpha-KO mice exhibited marked thinning of the retina and abnormal retinal vasculature. The pathologic changes in HIF-2alpha-KO mice were associated with a virtual absence of postreceptor function. The expression of a surrogate marker for HIF-2alpha mRNA localized to vascular endothelial, amacrine, and retinal pigment epithelial (RPE) cells. Several HIF-2alpha target genes involved in angiogenesis, retinal protection, and stress responses have altered expression patterns in HIF-2alpha-KO retinas.
  
  
  CONCLUSIONS
  HIF-2alpha-KO mice exhibit marked retinopathy consistent with complete loss of vision by 1 month of age. Impaired HIF-2alpha signaling in HIF-2alpha-KO mice likely produces functional deficits in cell types in which HIF-2alpha normally is expressed, ultimately resulting in retinopathy. Future studies will address whether the molecular abnormalities described in this study are directly responsible for the retinal disease in HIF-2alpha-KO mice.
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
authors.forename: Kan
authors.initials: K
authors.lastname: Ding
authors.forename: Marzia
authors.initials: M
authors.lastname: Scortegagna
authors.forename: Robyn
authors.initials: R
authors.lastname: Seaman
authors.forename: David G
authors.initials: DG
authors.lastname: Birch
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Garcia
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D004596:Electroretinography; D005260:Female; D017353:Gene Deletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity; D012160:Retina / Q000502:physiology; D012164:Retinal Diseases / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000172:deficiency* / Q000235:genetics; D014786:Vision Disorders / Q000209:etiology / Q000503:physiopathology; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015534:Trans-Activators; D000099162:Endothelial PAS Domain-Containing Protein 1