The role of crumbs genes in the vertebrate cornea

Beyer, J., Zhao, X.C., Yee, R., Khaliq, S., McMahon, T.T., Ying, H., Yue, B.Y., and Malicki, J.J.
Investigative ophthalmology & visual science   51(9): 4549-4556 (Journal)
Registered Authors
Malicki, Jarema, Zhao, Xinping
MeSH Terms
  • Animals
  • Cell Polarity/physiology
  • Epithelial Cells/pathology
  • Epithelial Cells/physiology
  • Epithelial Cells/ultrastructure
  • Epithelium, Corneal/abnormalities*
  • Epithelium, Corneal/pathology
  • Epithelium, Corneal/physiology*
  • Eye Proteins/genetics*
  • Eye Proteins/metabolism
  • Female
  • Gene Expression Regulation, Developmental*
  • Heterozygote
  • Humans
  • Immunohistochemistry
  • Male
  • Membrane Proteins/genetics*
  • Membrane Proteins/metabolism
  • Microscopy, Electron
  • Nerve Tissue Proteins/genetics*
  • Nerve Tissue Proteins/metabolism
  • Pedigree
  • Polymerase Chain Reaction
  • Severity of Illness Index
  • Stromal Cells/pathology
  • Stromal Cells/physiology
  • Stromal Cells/ultrastructure
  • Vertebrates
  • Zebrafish
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
20805571 Full text @ Invest. Ophthalmol. Vis. Sci.
PURPOSE: To evaluate the role of crumbs genes and related epithelial polarity loci in the vertebrate cornea. METHODS: The authors used histologic analysis and electron microscopy to evaluate the corneas of zebrafish mutant for a crumbs locus oko meduzy (ome) and in mutants of four other loci, nagie oko (nok), heart and soul (has), mosaic eyes (moe), and ncad (formerly glass onion), that function in the same or related genetic pathways. In parallel, they performed an evaluation of corneas in human carriers of a crumbs gene, CRB1, and mutations using topography and biomicroscopy. The expression of the CRB1 gene in the normal human cornea was examined by polymerase chain reaction (PCR) and immunohistochemical staining. RESULTS: The corneas of zebrafish mutants display severe abnormalities of the epithelial and stromal layers. The epithelial cells do not properly adhere to each other, and fluid-filled spaces form between them. In addition, the layering of the corneal stroma is poorly formed or absent. The corneas of human carriers of CRB1 mutations display shape deviations compared with what has been observed in normal individuals. A PCR product of the correct size was obtained from normal human corneal samples. Sequence analyses confirmed its identity to be the human CRB1 gene. Immunohistochemical staining using anti-CRB1 yielded positive brown deposits in the human cornea. CONCLUSIONS: crumbs genes play a role in the differentiation of the vertebrate cornea. Corneal defects associated with crumbs gene mutations are very severe in the zebrafish model and, in comparison, appear clinically less pronounced in the human eye.
Genes / Markers
Show all Figures
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes