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Molecular and Cellular Biology, January 2007, p. 182-194, Vol. 27, No. 1
0270-7306/07/$08.00+0     doi:10.1128/MCB.00846-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Conditional Deletion of the Mouse Klf4 Gene Results in Corneal Epithelial Fragility, Stromal Edema, and Loss of Conjunctival Goblet Cells{triangledown} ,{dagger}

Shivalingappa K. Swamynathan,1* Jonathan P. Katz,2 Klaus H. Kaestner,3 Ruth Ashery-Padan,4 Mary A. Crawford,5 and Joram Piatigorsky1

Laboratory of Molecular and Developmental Biology, NEI, NIH, Bethesda, Maryland,1 Division of Gastroenterology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania,2 Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania,3 Department of Human Genetics and Molecular Medicine, Tel Aviv University, Tel Aviv, Israel,4 Laboratory of Immunology, NEI, NIH, Bethesda, Maryland5

Received 11 May 2006/ Returned for modification 5 July 2006/ Accepted 6 October 2006

The Krüppel-like transcription factor KLF4 is among the most highly expressed transcription factors in the mouse cornea (B. Norman, J. Davis, and J. Piatigorsky, Investig. Ophthalmol. Vis. Sci. 45:429-440, 2004). Here, we deleted the Klf4 gene selectively in the surface ectoderm-derived structures of the eye (cornea, conjunctiva, eyelids, and lens) by mating Klf4-LoxP mice (J. P. Katz, N. Perreault, B. G. Goldstein, C. S. Lee, P. A. Labosky, V. W. Yang, and K. H. Kaestner, Development 129:2619-2628, 2002) with Le-Cre mice (R. Ashery-Padan, T. Marquardt, X. Zhou, and P. Gruss, Genes Dev. 14:2701-2711, 2000). Klf4 conditional null (Klf4CN) embryos developed normally, and the adult mice were viable and fertile. Unlike the wild type, the Klf4CN cornea consisted of three to four epithelial cell layers; swollen, vacuolated basal epithelial and endothelial cells; and edematous stroma. The conjunctiva lacked goblet cells, and the anterior cortical lens was vacuolated in Klf4CN mice. Excessive cell sloughing resulted in fewer epithelial cell layers in spite of increased cell proliferation at the Klf4CN ocular surface. Expression of the keratin-12 and aquaporin-5 genes was downregulated, consistent with the Klf4CN corneal epithelial fragility and stromal edema, respectively. These observations provide new insights into the role of KLF4 in postnatal maturation and maintenance of the ocular surface and suggest that the Klf4CN mouse is a useful model for investigating ocular surface pathologies such as dry eye, Meesmann's dystrophy, and Steven's-Johnson syndrome.

* Corresponding author. Mailing address: Lab. Mol. Dev. Biol., National Eye Institute, NIH, 7 Memorial Drive, Room 129, Bethesda, MD 20892. Phone: (301) 402-4535. Fax: (301) 435-7678. E-mail: Swamynathans{at}nei.nih.gov.

{triangledown} Published ahead of print on 23 October 2006.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, January 2007, p. 182-194, Vol. 27, No. 1
0270-7306/07/$08.00+0     doi:10.1128/MCB.00846-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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