Conditional disruption of mouse Klf5 results in defective eyelids with malformed meibomian glands, abnormal cornea and loss of conjunctival goblet cells

Department of Ophthalmology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Developmental Biology (Impact Factor: 3.55). 05/2011; 356(1):5-18. DOI: 10.1016/j.ydbio.2011.05.005
Source: PubMed


Members of the Krüppel-like family of transcription factors regulate diverse developmental processes in various organs. Previously, we have demonstrated the role of Klf4 in the mouse ocular surface. Herein, we determined the role of the structurally related Klf5, using Klf5-conditional null (Klf5CN) mice derived by mating Klf5-LoxP and Le-Cre mice. Klf5 mRNA was detected as early as embryonic day 12 (E12) in the cornea, conjunctiva and eyelids, wherein its expression increased during development. Though the embryonic eye morphogenesis was unaltered in the Klf5CN mice, postnatal maturation was defective, resulting in smaller eyes with swollen eyelids that failed to separate properly. Klf5CN palpebral epidermis was hyperplastic with 7-9 layers of keratinocytes, compared with 2-3 in the wild type (WT). Klf5CN eyelid hair follicles and sebaceous glands were significantly enlarged, and the meibomian glands malformed. Klf5CN lacrimal glands displayed increased vasculature and large number of infiltrating cells. Klf5CN corneas were translucent, thicker with defective epithelial basement membrane and hypercellular stroma. Klf5CN conjunctiva lacked goblet cells, demonstrating that Klf5 is required for conjunctival goblet cell development. The number of Ki67-positive mitotic cells was more than doubled, consistent with the increased number of Klf5CN ocular surface epithelial cells. Co-ablation of Klf4 and Klf5 resulted in a more severe ocular surface phenotype compared with Klf4CN or Klf5CN, demonstrating that Klf4 and Klf5 share few if any, redundant functions. Thus, Klf5CN mice provide a useful model for investigating ocular surface pathologies involving meibomian gland dysfunction, blepharitis, corneal or conjunctival defects.


Available from: Shivalingappa Swamynathan, Mar 11, 2014
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    • "Notably, this threshold also appeared to eliminate signals derived from the minimal amount of contamination from neighboring tissues that is, to some extent, inevitable during murine embryonic lens isolation. For example, the expression of the Krüppel-like transcription factors Klf4 and Klf5, which are abundant in the corneal epithelium [14] [15], was detected at 0.48 RPKM and 0.09 RPKM respectively, while those for platelet endothelial cell adhesion molecule 1 (Pecam1), a marker expressed abundantly in blood vessels [16] "
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    • "In previous publications using the same expression chips, a N 1.5-fold change combined with P b .05 has been defined as the minimum meaningful fold change in the identification of differentially expressed genes333435. Application of the same principle to our data resulted in a total of 1197 genes, 569 of which were upregulated and 628 were downregulated (Table S2). To evaluate the quality of the microarray data, we selected 33 genes with different degrees of differential expression in the microarray analysis and performed real-time RT-PCR in four to eight wild-type or Klf5-null DPs. "
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    • "Foxc1 mediates the BMP signaling required for lacrimal gland development (Mattiske et al., 2006). Klf5 conditional null lacrimal glands showed a disrupted acinar organization (Kenchegowda et al., 2011) and Six1 −/− fetuses displayed small lacrimal glands (Laclef et al., 2003). However, little is known about the mechanisms required to initiate lacrimal gland formation by FGF signaling. "
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