1.Gene expression profiling of light-induced retinal degeneration in phototransduction gene knockout mice.
Jayalakshmi KRISHNAN ; Jiayan CHEN ; Kum Joo SHIN ; Jong Ik HWANG ; Sang Uk HAN ; Gwang LEE ; Sangdun CHOI
Experimental & Molecular Medicine 2008;40(5):495-504
Exposure to light can induce photoreceptor cell death and exacerbate retinal degeneration. In this study, mice with genetic knockout of several genes, including rhodopsin kinase (Rhok-/-), arrestin (Sag-/-), transducin (Gnat1-/-), c-Fos (c-Fos-/-) and arrestin/transducin (Sag-/-/Gnat1-/-), were examined. We measured the expression levels of thousands of genes in order to investigate their roles in phototransduction signaling in light-induced retinal degeneration using DNA microarray technology and then further explored the gene network using pathway analysis tools. Several cascades of gene components were induced or inhibited as a result of corresponding gene knockout under specific light conditions. Transducin deletion blocked the apoptotic signaling induced by exposure to low light conditions, and it did not require c-Fos/AP-1. Deletion of c-Fos blocked the apoptotic signaling induced by exposure to high intensity light. In the present study, we identified many gene transcripts that are essential for the initiation of light-induced rod degeneration and proposed several important networks that are involved in pro- and anti-apoptotic signaling. We also demonstrated the different cascades of gene components that participate in apoptotic signaling under specific light conditions.
Animals
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Apoptosis/radiation effects
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G-Protein-Coupled Receptor Kinase 1/genetics
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GTP-Binding Protein alpha Subunits/genetics
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*Gene Expression Profiling
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Genes, fos/genetics
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Light/adverse effects
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Light Signal Transduction/*genetics/physiology/radiation effects
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Mice
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Mice, Knockout
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Oligonucleotide Array Sequence Analysis
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Retina/metabolism/pathology/radiation effects
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Retinal Degeneration/etiology/*genetics/physiopathology
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Transducin/genetics