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Corneal morphogenesis during development and diseases.
Eye Contact Lens. 2010 Sep; 36(5):265-8.EC

Abstract

OBJECTIVE

To review the use of genetically modified mouse lines for elucidating corneal morphogenesis during embryonic development and diseases.

METHODS

Transgenesis and gene-targeting techniques were used to create doxycycline-inducible mouse models (tet-On) to express transgenes or ablation of LoxP-modified genes or both in corneal cells, e.g., epithelial cells, and keratocytes and periocular mesenchymal cells of neural crest origin.

RESULTS

Two driver mouse lines, i.e., Krt12-rtTA and Kera-rtTA, were created, which express reverse tetracycline transcription activator (rtTA) in corneal epithelial cells and keratocytes, respectively. Bitransgenic (Krt12-rtTA/tet-o-FGF7) and triple transgenic mice (Krt12rtTA/tet-o-Cre/Ctnnb1 and Kera-rtTA/tet-o-Cre/Ctnnb1) were obtained through cross-breeding tet-o-FGF7, tet-o-Cre, and Ctnnb1 mice. On doxycycline induction, overexpression of FGF7 by corneal epithelial cells of bitransgenic Krt12-rtTA/tet-o-FGF7 mice caused nuclear translocation of beta-catenin and epithelium hyperplasia resembling human ocular surface squamous neoplasia; in triple transgenic mice (Krt12rtTA/tet-o-Cre/Ctnnb1), constitutive nuclear translocation of mutant beta-catenin (loss of exon 3) leads to hyper proliferation of corneal epithelial cells; in comparison of expression of beta-catenin mutant protein by migrating, periocular mesenchymal cells of Kera-rtTA/tet-o-Cre/Ctnnb1 caused eyelid malformation.

CONCLUSIONS

Use of genetically modified mice is of great value to study the pathophysiology of ocular surface defects resulting from genetic mutations.

Authors+Show Affiliations

Department of Ophthalmology, College of Medicine, University of Cincinnati, Cincinnati, OH 45267-0838, USA. winston.kao@uc.edu

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20724850

Citation

Kao, Winston W-Y. "Corneal Morphogenesis During Development and Diseases." Eye & Contact Lens, vol. 36, no. 5, 2010, pp. 265-8.
Kao WW. Corneal morphogenesis during development and diseases. Eye Contact Lens. 2010;36(5):265-8.
Kao, W. W. (2010). Corneal morphogenesis during development and diseases. Eye & Contact Lens, 36(5), 265-8. https://doi.org/10.1097/ICL.0b013e3181ef0e00
Kao WW. Corneal Morphogenesis During Development and Diseases. Eye Contact Lens. 2010;36(5):265-8. PubMed PMID: 20724850.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Corneal morphogenesis during development and diseases. A1 - Kao,Winston W-Y, PY - 2010/8/21/entrez PY - 2010/8/21/pubmed PY - 2011/1/21/medline SP - 265 EP - 8 JF - Eye & contact lens JO - Eye Contact Lens VL - 36 IS - 5 N2 - OBJECTIVE: To review the use of genetically modified mouse lines for elucidating corneal morphogenesis during embryonic development and diseases. METHODS: Transgenesis and gene-targeting techniques were used to create doxycycline-inducible mouse models (tet-On) to express transgenes or ablation of LoxP-modified genes or both in corneal cells, e.g., epithelial cells, and keratocytes and periocular mesenchymal cells of neural crest origin. RESULTS: Two driver mouse lines, i.e., Krt12-rtTA and Kera-rtTA, were created, which express reverse tetracycline transcription activator (rtTA) in corneal epithelial cells and keratocytes, respectively. Bitransgenic (Krt12-rtTA/tet-o-FGF7) and triple transgenic mice (Krt12rtTA/tet-o-Cre/Ctnnb1 and Kera-rtTA/tet-o-Cre/Ctnnb1) were obtained through cross-breeding tet-o-FGF7, tet-o-Cre, and Ctnnb1 mice. On doxycycline induction, overexpression of FGF7 by corneal epithelial cells of bitransgenic Krt12-rtTA/tet-o-FGF7 mice caused nuclear translocation of beta-catenin and epithelium hyperplasia resembling human ocular surface squamous neoplasia; in triple transgenic mice (Krt12rtTA/tet-o-Cre/Ctnnb1), constitutive nuclear translocation of mutant beta-catenin (loss of exon 3) leads to hyper proliferation of corneal epithelial cells; in comparison of expression of beta-catenin mutant protein by migrating, periocular mesenchymal cells of Kera-rtTA/tet-o-Cre/Ctnnb1 caused eyelid malformation. CONCLUSIONS: Use of genetically modified mice is of great value to study the pathophysiology of ocular surface defects resulting from genetic mutations. SN - 1542-233X UR - https://www.unboundmedicine.com/medline/citation/20724850/Corneal_morphogenesis_during_development_and_diseases_ L2 - https://doi.org/10.1097/ICL.0b013e3181ef0e00 DB - PRIME DP - Unbound Medicine ER -