Lens-specific deletion of the gene increased apoptosis by enhancing the caspase-3/caspase-8 signaling pathway

Abstract

Objective To investigate the influence of Msx2 conditional gene knockout during lens development in mice. Methods Lens-specific Msx2 knockout mice were generated using the Cre -loxP system. The eyes of Msx2 conditional knockout ( Msx2 CKO) and wild-type ( Msx2 WT) mice were examined during embryonic and early postnatal periods using histological, immunofluorescence, in situ hybridization, cell proliferation, apoptosis, and mRNA microarray analyses. Results Msx2 CKO mice exhibited small lens formation and microphthalmia after birth, while Msx2 CKO embryos exhibited a persistent lens stalk, small lens formation, and microphthalmia. Conditional deletion of Msx2 also led to an increased apoptosis rate, a significant reduction in FoxE3 expression, and an upregulation of Prox1 expression in the lens vesicle during the early embryonic period. Microarray comparison of Msx2 CKO and Msx2 WT lens transcriptomes identified a large number of differentially expressed genes. Real-time PCR showed that Casp8 and Casp3 expression was upregulated in Msx2 CKO mice at post-natal day 1. Conclusion The activation of apoptosis through the caspase-8/caspase-3 signaling pathway, together with the downregulation of FoxE3 expression, appeared to account for the smaller lens formation in Msx2 CKO mice.