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Shylaja Hegde, Kiran Srivastava, Roy Joseph, Om Srivastava; A Potential Molecular Mechanism of Cataract Development in CRYAAN101D Transgenic Mice Compared to CRYAAWT Mice. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2967.
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© ARVO (1962-2015); The Authors (2016-present)
The purpose was to elucidate a potential molecular mechanism of cortical cataract development in a mouse model expressing deamidated of αA (deamidation at N101 position: αAN101D) compared to wild type transgenic mice (WT)
Previously we have shown that a mouse lens expressing deamidated alpha A- crystallin (αAN101D) develops mild cortical lens opacity by the age of 7-months compare to the age-matched lenses of mice expressing wild-type (WT) alpha A-transgene (J. Biol. Chem. 286:11579-11592, 2011). To examine the effects of crystallin deamidation (αA N101D transgene) on gene expression profile, whole genome transcriptome analysis (RNA seq) was carried out. Additionally, the relative expression levels of apoptotic genes in lenses of 3- and 5-months from both types of mice were examined by qRT-PCR and immunohistochemistry
The RNA Seq method identified several genes that were differentially expressed in 2- and 4-months old αAN101D mouse lenses relative to same aged WT mouse lenses. Most notable was the altered expression of several transcripts associated with cell death and cell structure and assembly in 4-months-old A N101D lenses. The qRT-PCR and immunohistochemical results revealed over expression of several pro-apoptotic markers such as Bax, Caspase-6 and Caspase-9 in αA N101D lenses, The TUNEL assay further confirmed apoptosis of epithelial cells at the bow region at 6-months and older lenses of αAN101D mice. Microscopic analysis provided additional evidence for delayed denucleation process and membrane disruption in αAN101D lenses
Relative to WT-mice, the lenses of αAN101D showed altered expression of transcripts involved in cell death and cell structure and assembly, and increased expression of apoptotic marker genes, suggesting apoptosis is a likely factor contributing to the development of cortical cataract in CRYAAN101D transgenic mouse
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