Department of Ophthalmology, 4th Affiliated Hospital of China Medical University, Eye Hospital of China Medical University, Key Laboratory of Lens Research of Liaoning Province, Shenyang 110005, China
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 were
documented. 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 at
E17.5 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 axial
diameter), 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.
Bardakjian TM, Schneider A. The genetics of anophthalmia and microphthalmia. Curr Opin Ophthalmol, 2011, 22(5): 309-313.DOI: 10.1097/ICU.0b013e328349b004.
[3]
Yasue A, Kono H, Habuta M, et al. Relationship between somatic mosaicism of Pax6 mutation and variable developmental eye abnormalities-an analysis of CRISPR genome-edited mouse embryos. Sci Rep, 2017, 7(1): 53. DOI: 10.1038/s41598-017-00088-w.
[4]
Cvekl A, Duncan MK. Genetic and epigenetic mechanisms of gene regulation during lens development. Prog Retin Eye Res,2007, 26(6): 555-597. DOI: 10.1016/j.preteyeres.2007.07.002.
Bensoussan V, Lallemand Y, Moreau J, et al. Generation of an Msx2-GFP Conditional Null Allele. Genesis, 2008, 46(5): 276-282. DOI: 10.1002/dvg.20390.
[7]
Ashery-Padan R, Marquardt T, Zhou X, et al. Pax6 activity in the lens primordium is required for lens formation and for correctplacement of a single retina in the eye. Genes Dev, 2000,14(21): 2701-2711. DOI:10.1101/gad.184000.
[8]
Zhao J, Kawai K, Wang H, et al. Loss of Msx2 function downregulates the FoxE3 expression and results in anterior segment dysgenesis resembling Peters anomaly. Am J Pathol, 2012,180(6): 2230-2239. DOI: 10.1016/j.ajpath.2012.02.017.
[9]
Garcia CM, Huang J, Madakashira BP, et al. The function of FGF signaling in the lens placode. Dev Biol, 2011, 351(1): 176-185. DOI: 10.1016/j.ydbio.2011.01.001.
[10]
Huang J, Liu Y, Filas B, et al. Negative and positive auto-regulation of BMP expression in early eye development. Dev Biol, 2015,407(2): 256-264. DOI: 10.1016/j.ydbio.2015.09.009.[11] Wu LY, Li M, Hinton DR, et al. Microphthalmia resulting from MSX2-induced apoptosis in the optic vesicle. Invest Ophthalmol Vis Sci, 2003, 44(6): 2404-2412.
[12]
Bensoussan-Trigano V, Lallemand Y, Saint CC, et al. Msx1 and Msx2 in limb mesenchyme modulate digit number and identity.Dev Dyn, 2011, 240(5): 1190-1202. DOI: 10.1002/dvdy.22619.
[1]
葛坚, 赵家良, 黎晓新. 眼科学. 2版. 北京: 人民卫生出版社，2005: 378.
[2]
Bardakjian TM, Schneider A. The genetics of anophthalmia and microphthalmia. Curr Opin Ophthalmol, 2011, 22(5): 309-313.DOI: 10.1097/ICU.0b013e328349b004.
[3]
Yasue A, Kono H, Habuta M, et al. Relationship between somatic mosaicism of Pax6 mutation and variable developmental eye abnormalities-an analysis of CRISPR genome-edited mouse embryos. Sci Rep, 2017, 7(1): 53. DOI: 10.1038/s41598-017-00088-w.
[4]
Cvekl A, Duncan MK. Genetic and epigenetic mechanisms of gene regulation during lens development. Prog Retin Eye Res,2007, 26(6): 555-597. DOI: 10.1016/j.preteyeres.2007.07.002.
Bensoussan V, Lallemand Y, Moreau J, et al. Generation of an Msx2-GFP Conditional Null Allele. Genesis, 2008, 46(5): 276-282. DOI: 10.1002/dvg.20390.
[7]
Ashery-Padan R, Marquardt T, Zhou X, et al. Pax6 activity in the lens primordium is required for lens formation and for correctplacement of a single retina in the eye. Genes Dev, 2000,14(21): 2701-2711. DOI:10.1101/gad.184000.
[8]
Zhao J, Kawai K, Wang H, et al. Loss of Msx2 function downregulates the FoxE3 expression and results in anterior segment dysgenesis resembling Peters anomaly. Am J Pathol, 2012,180(6): 2230-2239. DOI: 10.1016/j.ajpath.2012.02.017.
[9]
Garcia CM, Huang J, Madakashira BP, et al. The function of FGF signaling in the lens placode. Dev Biol, 2011, 351(1): 176-185. DOI: 10.1016/j.ydbio.2011.01.001.
[10]
Huang J, Liu Y, Filas B, et al. Negative and positive auto-regulation of BMP expression in early eye development. Dev Biol, 2015,407(2): 256-264. DOI: 10.1016/j.ydbio.2015.09.009.[11] Wu LY, Li M, Hinton DR, et al. Microphthalmia resulting from MSX2-induced apoptosis in the optic vesicle. Invest Ophthalmol Vis Sci, 2003, 44(6): 2404-2412.
[12]
Bensoussan-Trigano V, Lallemand Y, Saint CC, et al. Msx1 and Msx2 in limb mesenchyme modulate digit number and identity.Dev Dyn, 2011, 240(5): 1190-1202. DOI: 10.1002/dvdy.22619.
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