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S.K. Swamynathan, K. Kaestner, R. Ashery–Padan, J. Piatigorsky; Regulation of Murine Eye Development by Kruppel–Like Transcription Factor KLF4 . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3009.
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Kruppel–like transcription factor KLF4 is one of the most highly expressed transcription factors in both embryonic and adult mouse and human corneal epithelial cells. Since KLF4 null mice die within 15 hours of birth, they are not useful to study the role of KLF4 in development of mature cornea which continues till 6 weeks after birth. In this study, we have generated KLF4 conditional null mice to investigate the function of KLF4 during development of mouse cornea.
Conditional null mice lacking KLF4 specifically in the developing eye were generated by mating KLF4–LoxP mice (Katz et al, 2002. Development 129:2619–28) with Le–Cre mice (Ashery–Padan et al, 2000. Genes Dev. 14:2701–11) expressing Cre recombinase in the developing eye. Histology and ultrastructure of the KLF4 conditional null mice eyes were analyzed by conventional microscopy and scanning as well as transmission electron microscopy.
KLF4 conditional null eyes were microphthalmic with a rough, speckled appearance upon visual inspection. Hematoxylin and eosin stained sections revealed that the KLF4 conditional null cornea had only 3–4 (instead of 5–7) epithelial cell layers, abnormally swollen basal epithelial cells and edematous stroma. Transmission electron microscopy showed that the corneal surface epithelial cells of KLF4 conditional null mice are loosely attached with a reduced number of connecting desmosomes. Scanning electron microscopy demonstrated that the KLF4 conditional null corneal surface possessed cells with variable darkness in contrast to the uniformly dark cells on the wild type corneal surface. In addition, the KLF4 conditional null mice possessed hyperplastic iris and a spongy lens covered by a thinner lens capsule with many vacuoles beneath the lens epithelium. Analysis of changes in gene expression in the KLF4 conditional null corneas is in progress.
KLF4 plays a critical role during development of mouse corneal epithelium, stroma, as well as iris and lens.
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