Gene expression profiling of light-induced retinal degeneration in phototransduction gene knockout mice.
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.
Krishnan
Jayalakshmi
J
Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Korea.
Chen
Jiayan
J
Shin
Kum Joo
KJ
Hwang
Jong Ik
JI
Han
Sang Uk
SU
Lee
Gwang
G
Choi
Sangdun
S
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D051606:G-Protein-Coupled Receptor Kinase 1 / Q000235:genetics; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics; D020869:Gene Expression Profiling; D016762:Genes, fos / Q000235:genetics; D008027:Light / Q000009:adverse effects; D055537:Light Signal Transduction / Q000235:genetics* / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D012160:Retina / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D012162:Retinal Degeneration / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D015293:Transducin / Q000235:genetics
D044385:GTP-Binding Protein alpha Subunits; C488949:Gnat1 protein, mouse; D051606:G-Protein-Coupled Receptor Kinase 1; D015293:Transducin