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.
Pub Type(s)
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
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 -
