小鼠肌节同源盒基因同系物2条件性敲除在先天性白内障发生中的作用

目的：研究晶状体中肌节同源盒基因同系物2（Msx2）条件性基因敲除与先天性白内障发生的关系。方法：实验研究。选取条件性基因敲除小鼠Msx2CKO（Msx2fl/fl/Le-Cre+）为实验组，野生型小鼠Msx2WT（Msx2fl/fl）为对照组。取胚胎17.5 d（E17.5）Msx2WT小鼠胚胎头部组织作冰冻切片，采用RNA原位分子杂交方法检测Msx2在眼组织内的正常表达。取2 组小鼠E17.5 和生后8 d（P8）眼球组织石蜡切片HE染色观察晶状体组织形态学变化。比较2 月龄Msx2CKO和Msx2WT小鼠晶状体质量和直径，组间比较采用独立样本t检验。结果：本研究观察到超过50%的2 月龄Msx2CKO小鼠眼部出现角膜轻微混浊，晶状体变小(质量和直径)，晶状体混浊及小眼球畸形。石蜡切片HE染色观察到Msx2CKO E17.5及P8小鼠晶状体内分化的纤维细胞排列紊乱，赤道部晶状体上皮细胞及邻近的纤维细胞中有空泡，排列明显紊乱。2月龄Msx2CKO组小鼠的直径小于Msx2WT组小鼠（t=4.80，P < 0.05），重量小于后者（t=14.29，P < 0.05）。结论：Msx2基因对小鼠晶状体发育起重要的调控作用，晶状体条件性敲除该基因可引起先天性白内障发生。

The Effects of msh Homeobox 2 Conditional Knockout on Congenital Cataract Formation in Mice

Objective: We investigated the relationship between msh homeobox 2 (Msx2) conditional deletion and congenital cataract formation. Methods: In this experimental study, development of the ocular lens in Msx2CKO (Msx2fl/fl/Le-Cre+) and control Msx2WT (Msx2fl/fl) embryos and postnatal mice weredocumented. Embryo heads at E17.5 (late embryo stage) were fixed, and frozen sections were processed for RNA in situ hybridization for detecting normal Msx2 expression. Morphological and histological differences were detected by hematoxylin and eosin staining of lenses from Msx2CKO and Msx2WT atE17.5 and P8 (8 days parturition). Lens axis diameter and weight were examined between Msx2CKO and Msx2WT mice at 2 months old. Statistical analyses were performed by independent t-tests. Results: More than 50% of the Msx2CKO mice exhibited minor corneal opacity, small lens formation (weight and axialdiameter), nuclear sclerotic cataract, and microphthalmia compared with the wild-type littermates at two months. Msx2CKO embryos and postnatal specimens had differentiated lens fibers that were disorganized, and equatorial lens epithelial cells and lens fibers were vacuolated. Lens axis diameter in Msx2CKO micewas smaller than in Msx2WT mice, and weight was lighter in Msx2CKO mice than in Msx2WT mice.Conclusions: The Msx2 gene plays an important regulatory role during mouse lens development, and conditional deletion of Msx2 may cause congenital cataract formation.