title: Gene expression profiling of light-induced retinal degeneration in phototransduction gene knockout mice.
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.
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Korea.
authors.forename: Jayalakshmi
authors.initials: J
authors.lastname: Krishnan
authors.forename: Jiayan
authors.initials: J
authors.lastname: Chen
authors.forename: Kum Joo
authors.initials: KJ
authors.lastname: Shin
authors.forename: Jong Ik
authors.initials: JI
authors.lastname: Hwang
authors.forename: Sang Uk
authors.initials: SU
authors.lastname: Han
authors.forename: Gwang
authors.initials: G
authors.lastname: Lee
authors.forename: Sangdun
authors.initials: S
authors.lastname: Choi
mesh_terms: 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
chemical_list: D044385:GTP-Binding Protein alpha Subunits; C488949:Gnat1 protein, mouse; D051606:G-Protein-Coupled Receptor Kinase 1; D015293:Transducin