Gene expression profiling of light-induced retinal degeneration in phototransduction gene knockout mice

Exp Mol Med. 2008 Oct 31;40(5):495-504. doi: 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.

Publication types

  • Research Support, Non-U.S. Gov't

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*
  • Light Signal Transduction / physiology
  • Light Signal Transduction / radiation effects
  • Mice
  • Mice, Knockout
  • Oligonucleotide Array Sequence Analysis
  • Retina / metabolism
  • Retina / pathology
  • Retina / radiation effects
  • Retinal Degeneration / etiology
  • Retinal Degeneration / genetics*
  • Retinal Degeneration / physiopathology
  • Transducin / genetics

Substances

  • GTP-Binding Protein alpha Subunits
  • Gnat1 protein, mouse
  • G-Protein-Coupled Receptor Kinase 1
  • Transducin