title: Retinal pigment epithelium abnormalities in mice with adenomatous polyposis coli gene disruption.
abstract: OBJECTIVE
  To examine eyes from mice with targeted adenomatous polyposis coli (APC) gene disruption to determine if retinal pigment epithelium (RPE) abnormalities replicate the human counterpart.
  
  
  METHODS
  Thirty-two eyes from 16 mice heterozygous for APC gene disruption (chain-termination mutation in codon 1638 of exon 15) and 12 control eyes were examined by light microscopy.
  
  
  RESULTS
  Fifteen of 32 eyes from 12 of 16 APC-disrupted mice demonstrated abnormalities of the RPE and retina. The RPE abnormalities included RPE coloboma, unifocal and multifocal RPE hypertrophy, RPE hyperplasia, and RPE duplication with invasion in the areas of outer and inner segments. Retinal abnormalities included outer nuclear layer duplication and outer nuclear layer atrophy. There were no RPE and retinal abnormalities seen in the control eyes.
  
  
  CONCLUSIONS
  This study is consistent with the hypothesis that the APC gene is critical in the regulation of RPE proliferation and development. These findings also demonstrate that mutation of the APC gene in codon 1638, a location beyond the previously described critical region for human RPE abnormalities, leads to perturbation in the mouse RPE and retina. Further study of this murine model and the APC/RPE relationship may provide insight into regulatory mechanisms for RPE proliferation.
authors.affiliation: Department of Ophthalmology, Medical College of Georgia, Augusta, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Marcus
authors.forename: A K
authors.initials: AK
authors.lastname: Rustgi
authors.forename: D
authors.initials: D
authors.lastname: Defoe
authors.forename: S E
authors.initials: SE
authors.lastname: Brooks
authors.forename: R S
authors.initials: RS
authors.lastname: McCormick
authors.forename: T P
authors.initials: TP
authors.lastname: Thompson
authors.forename: W
authors.initials: W
authors.lastname: Edelmann
authors.forename: R
authors.initials: R
authors.lastname: Kucherlapati
authors.forename: S
authors.initials: S
authors.lastname: Smith
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D025601:Adenomatous Polyposis Coli Protein; D000818:Animals; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D017491:Genes, APC / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D010857:Pigment Epithelium of Eye / Q000002:abnormalities* / Q000473:pathology; D012160:Retina / Q000002:abnormalities / Q000473:pathology; D012164:Retinal Diseases / Q000235:genetics / Q000473:pathology
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D003598:Cytoskeletal Proteins