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W. Paper, M. Kroeber, S. Heersink, K. E. Ramsey, D. A. Stephan, P. Russell, E. R. Tamm; Elevated Amounts of Myocilin in the Aqueous Humor of Transgenic Mice Lead to Significant Changes in Ocular Gene Expression. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5918.
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To determine in vivo genomic expression changes in ocular tissues of transgenic ßB1-crystallin-Myoc mice with a substantial (4.7 ± 1.8-fold) increase of secreted myocilin in the aqueous humor (Zillig et al., IOVS 2005). Myocilin is a secreted glycoprotein that is mutated in some forms of primary open-angle glaucoma (POAG).
RNA was isolated from ocular tissues (without lens) of ßB1-crystallin-Myoc mice and wild-type littermates. Changes in gene expression were determined by hybridization of gene microarrays (Affymetrix Mouse 430 2.0), and confirmed by real-time RT-PCR, western blotting and immunohistochemistry.
Although ßB1-crystallin-Myoc mice do not express an overt phenotype, a substantial up- and downregulation of several distinct genes was found when compared to gene expression in wild-type littermates. A substantial upregulation was observed for Spon2 mRNA, which codes for an extracellular matrix protein involved in cellular adhesion. Prominent examples of downregulation were Was1, a gene which is involved in the regulation of actin polymerization, Ceacam1, which plays a role in cell-cell adhesion, and Six1, a transcription factor involved in development of eye and brain.
In vivo gene expression of ocular tissues changes in response to higher amounts of myocilin. The identification and functional analysis of differentially expressed genes will facilitate to understand the biological function(s) of myocilin and its role in POAG.
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