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首页> 外文期刊>Molecular and Cellular Biology >Conditional Deletion of the Mouse Klf4 Gene Results in Corneal Epithelial Fragility, Stromal Edema, and Loss of Conjunctival Goblet Cells
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Conditional Deletion of the Mouse Klf4 Gene Results in Corneal Epithelial Fragility, Stromal Edema, and Loss of Conjunctival Goblet Cells

机译：小鼠Klf4基因的条件删除导致角膜上皮脆性，间质水肿和结膜杯状细胞丢失

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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.
机译：Krüppel样转录因子KLF4是小鼠角膜中表达最高的转录因子之一（B.Norman，J.Davis和J.Piatigorsky，Investig.Ophthalmol.Vis.Sci.45：429-440，2004）。在这里，我们通过与 Klf4-LoxP 小鼠（JP）交配，选择性地删除了眼睛的外胚层表面结构（角膜，结膜，眼睑和晶状体）中的 Klf4 基因。 Katz，N.Perreault，BG Goldstein，CS Lee，PA Labosky，VW Yang和KH Kaestner，Development 129：2619-2628，2002），带有 Le-Cre 小鼠（R. Ashery-Padan， T.Marquardt，X.Zhou和P.Gruss，Genes Dev.14：2701-2711，2000）。 Klf4 条件性空（ Klf4 CN）胚胎正常发育，成年小鼠具有活力和繁殖力。与野生型不同， Klf4 CN角膜由三到四个上皮细胞层组成。肿胀，空泡的基底上皮和内皮细胞;和水肿的基质。结膜中缺少杯状细胞，并且 Klf4 CN小鼠的前皮质晶状体被空泡化。尽管 Klf4 CN眼表层细胞增殖增加，但过度脱落会导致上皮细胞层减少。角蛋白12和水通道蛋白5基因的表达下调，分别与 Klf4 CN角膜上皮脆性和基质水肿相一致。这些观察结果提供了有关KLF4在产后成熟和眼表维护中的作用的新见解，并表明 Klf4 CN小鼠是研究眼表病理​​学（如干眼症，Meesmann营养不良，和史蒂文·约翰逊综合症。

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