Project description:To understand the global view of dysregulated genes and pathwyas in CRYAAN101D lenses, RNA sequencing of 2 & 4 months old CRYAAWT and CRYAAN101D lenses was carried out.
Project description:To understand the global view of dysregulated genes and pathwyas in CRYAAN101D lenses, RNA sequencing of 2 & 4 months old CRYAAWT and CRYAAN101D lenses was carried out. Determination of differential gene expression between CRYAAWT and CRYAAN101D in 2 & 4 months old lenses
Project description:The Dbl family of proteins represents a large group of proto-oncogenes involved in cell growth regulation. Alterations of the normal function of these proteins lead to pathological processes such as developmental disorders and neoplastic transformation. We have generated transgenic mice introducing the onco-Dbl cDNA sequences linked to the metallothionein promoter into the germ line of FVB mice and found that onco-Dbl expression affected proliferation, migration and differentiation of lens epithelial cells. We used high density oligonucleotide microarray to define the transcriptional profile induced by Dbl in the lenses of transgenic mice and observed modulation of genes encoding proteins promoting epithelial-mesenchymal transition (EMT). Moreover, genes encoding proteins involved in the positive regulation of apoptosis were markedly down regulated while anti-apoptotic genes were strongly up-regulated. Finally, several genes encoding proteins involved in the process of angiogenesis were up-regulated. These observations were validated by histological and immunohistochemical examination of the transgenic lenses, where vascularization can be readily observed. Thus, onco-Dbl expression in mouse lenses induces disruption of the lens architecture, epithelial cell proliferation, EMT, evasion from cell death, and aberrant angiogenesis. Whole lenses were removed from 2, 14, and 42 day old Dbl transgenic and wild type mice. 4 to 8 individual lenses were pooled . Three independent pools from each time and condition were used as replicates.
Project description:The E2F family consists of transcriptional repressors and activators that control cell proliferation. In the classic paradigm of cell cycle regulation, the three activators, E2F1, E2F2 and E2F3, are invariably depicted as the final components of a CDK/Rb signaling cascade that executes the transcriptional program necessary to commit cells to enter S phase. Unexpectedly, we find through analysis of Affymetrix expression array data that mature lens epithelial cells deficient for E2F1-3 fail to repress cell cycle-regulated genes (and other targets of E2F) and that this corresponds with subsequent apoptosis and cellular collapse in the lens. Murine lenses were collected at two stages of development for RNA extraction and hybridization on Affymetrix microarrays. Our aim was to determine key events that lead to cellular collapse of lenses triply deficient for E2F1, E2F2, and E2F3 in neonates.
Project description:The addition of 2ME2 (HIF-1 inhibitor) to rat model of galactose-induced cataract decreased opacity and therapeutic effect. Genes regulated by 2ME2 addition were identified by microarray analysis. A total of 7 samples were analyzed: samples with no cataract (Control_Day4, Control_Day6), samples with cataract (Galactose-1, Galactose-2, Galactose-3), samples with decreased lens opacity (2ME2, 2ME2-2)
