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X. Xu, E. Kudryavtseva, J. Mannik, J. Spencer, B. Andersen; Involvement of LIM-domain Cofactor Clim/Ldb in Corneal Homeostasis. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2727.
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Co-factors of LIM domains (Clim/Ldb), which were originally identified as co-factors of LIM-homeodomain and LIM-only transcription factors, are thought to function as adaptors that facilitate the assembly of transcriptional complexes. Because Clim2 is expressed extensively in various epithelial tissues, we investigated its role in the regulation of epithelial homeostasis.
We generated transgenic mice expressing a dominant-negative Clim (DN-Clim) under control of the keratin (K) 14 promoter. Mice were analyzed with histology, immunohistochemistry and electron microscopy.
The K14-DN-Clim mice developed striking corneal abnormalities in addition to progressive hair loss. Newborn K14-DN-Clim mice developed corneal stromal edema and epithelial blisters. Later, corneal wounds with leukocyte infiltration and neovascularization developed, presumably due to rupture of the blisters. As the mice aged, thinning of the corneal epithelium was observed, suggesting the possibility of a stem cell deficiency; DN-Clim is expressed in the corneal epithelial stem cell compartment of the limbus region. Finally, the corneal epithelium in transgenic mice acquired epidermal properties. Transmission electron microscopy indicates that altered hemidesmosome structures may be the cause of corneal blisters.
Our study suggests that Clim co-factors are important for the homeostasis of cornea; specifically, we propose that Clims are involved in the regulation of genes required for adhesion of corneal epithelial cells as well as stem cell maintenance. The K14-DN-Clim mice provide a new mouse model that exhibits several features that characterize corneal diseases, and may be useful for testing therapeutic approaches to corneal diseases.
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