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M Hayashi, C-Y Liu, Y Hayashi, J Tichelaar, JA Whitsett, WW Kao; Induction of Corneal Epithelial Hypertrophy by FGF-7 in a Binary Inducible Transgenic Mouse Model . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1649.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To establish a binary inducible transgenic mouse model that can be used to elucidate the roles of growth factors, e.g., FGF-7, on corneal biology. It has been suggested that FGF-7 (KGF, keratinocyte growth factor) serves as a paracrine that modulates the growth of corneal epithelial cell. The present studies are to investigate the effect of excess FGF-7 on corneal epithelial cells in a binary tetracycline inducible transgenic mouse line. Methods: A keratocyte-specific 3.2 kb murine keratocan promotor (Kerapr) has been used to prepare Kerapr-rtTA transgenic (KeraprrtTA/+) mice that constitutively overexpress rtTA (reverse tetracycline transcription activator) in cornea. The KeraprrtTA/+ mice were crossed with tet-OFGF7/FGF7 mice to produce compound heterozygous transgenic (KeraprrtTA/+•tet-OFGF7/+) mice, which were fed doxycycline water (0.5 mg/ml) for one week. The experimental mice were i.p. injected with BrdU (100 µg/g body weight) 2 h prior to sacrifice. The enucleated eyes were subjected to immunohistochemistry with anti-BrdU and anti K12 keratin antibodies. Results: There are about 30 and 11 BrdU-labeled corneal epithelial cells per corneal section prepared from compound heterozygous KeraprrtTA/+•tet-OFGF7/+ and simple tet-OFGF7/+ transgenic mice fed doxycycline, respectively. The expression pattern of K12 keratin is the same between the compound and simple transgenic mice. Conclusions: We have successfully established a cornea-specific KeraprrtTA/+ transgenic mouse line that can be used to prepare the binary tetracycline inducible transgenic mouse lines by mating with tet-Oreporter transgenic mice, which can be used to investigate the roles of various reporter genes, e.g., growth factors on corneal morphogenesis during development and maintenance of homeostasis in adults. Induction of FGF-7 expression by doxycycline enhances the corneal epithelial proliferation, but does not perturb the expression pattern of K12 keratin.
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