Exp Mol Med.
2008 Oct;40(5):495-504. 10.3858/emm.2008.40.5.495.
Gene expression profiling of light-induced retinal degeneration in phototransduction gene knockout mice
- Affiliations
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- 1Department of Molecular Science and Technology, Ajou University, Suwon, Korea. glee@ajou.ac.kr
- 2Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, CA 90033, USA.
- 3Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
- 4Graduate School of Medicine, Korea University, Seoul, Korea.
- 5Department of Surgery, College of Natural Science, Ajou University, Suwon, Korea.
- 6Brain Disease Research Center, Ajou University School of Medicine, Suwon, Korea.
- 7Department of Biological Sciences, College of Natural Science, Ajou University, Suwon, Korea.
- KMID: 1104803
- DOI: http://doi.org/10.3858/emm.2008.40.5.495
Abstract
- 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.
Keyword
MeSH Terms
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Animals
Apoptosis/radiation effects
G-Protein-Coupled Receptor Kinase 1/genetics
GTP-Binding Protein alpha Subunits/genetics
*Gene Expression Profiling
Genes, fos/genetics
Light/adverse effects
Light Signal Transduction/*genetics/physiology/radiation effects
Mice
Mice, Knockout
Oligonucleotide Array Sequence Analysis
Retina/metabolism/pathology/radiation effects
Retinal Degeneration/etiology/*genetics/physiopathology
Transducin/genetics
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