Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.
Invest Ophthalmol Vis Sci. 2010 Feb;51(2):795-803. doi: 10.1167/iovs.08-3327. Epub 2009 Sep 24.
The Pbx TALE (three-amino-acid loop extension) homeodomain proteins interact with class 1 Hox proteins, which are master regulators of cell fate decisions. This study was performed to elucidate the role of the Pbx1 TALE protein in the corneal epithelium of mice.
Pbx1(f/f) mice were crossed with mice containing Cre recombinase under the control of the K14 promoter. Subsequently, the eyes of these mice were dissected and prepared for histologic or molecular analysis.
Tissue-specific deletion of Pbx1 in the corneal epithelium of mice resulted in corneal dystrophy and clouding that was apparent in newborns and progressively worsened with age. Thickening of the cornea epithelium was accompanied by stromal infiltration with atypical basal cells, severe disorganization of stromal collagen matrix, and loss of corneal barrier function. High epithelial cell turnover was associated with perturbed expression of developmental regulators and aberrant differentiation, suggesting an important function for Pbx1 in determining corneal identity.
These studies establish an essential role of the Pbx1 proto-oncogene in corneal morphogenesis.
Pbx TALE（三氨基酸环延伸）同源结构域蛋白与 Hox 蛋白家族 1 成员相互作用，后者是细胞命运决定的主调控因子。本研究旨在阐明 Pbx1 TALE 蛋白在小鼠角膜上皮中的作用。
将 Pbx1(f/f) 小鼠与在 K14 启动子控制下表达 Cre 重组酶的小鼠进行杂交。随后，对这些小鼠的眼睛进行解剖并进行组织学或分子分析。
在小鼠角膜上皮中特异性敲除 Pbx1 导致角膜营养不良和混浊，这种现象在新生儿中明显，并随年龄增长而逐渐加重。角膜上皮增厚伴有基质中不典型基底细胞浸润、基质胶原基质严重紊乱以及角膜屏障功能丧失。高上皮细胞更新伴随着发育调节剂表达失调和异常分化，提示 Pbx1 在确定角膜特性方面具有重要功能。
这些研究确立了 Pbx1 原癌基因在角膜形态发生中的重要作用。
