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
  • 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.

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

arrestin; gene expression profiling; oligonucleotide array sequence analysis; proto-oncogene proteins c-fos; retinal degeneration; transducin

MeSH Terms

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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