The Association of COG5 and SRD5A3 Gene Mutations to ER Stress Activation and their Role in Retinal Degeneration
Year: 2018
Type: dissertation
Abstract: Five individuals were diagnosed with Leber’s congenital amaurosis, an early-onset inherited vision disorder. Two unrelated individuals have a homozygous mutation in SRD5A3 (p.W19X). The remaining three are siblings that have compound heterozygous mutations in COG5 (p.M32R; p.S777Q_fs*14). Both SRD5A3 and COG5 play critical roles in glycosylation, which if disrupted could result in ER stress. Transfection of wild-type or mutant variants of SRD5A3 or COG5 in vitro found no link between SRD5A3 and ER stress. However, PERK was significantly upregulated in response to compound transfection of the mutant COG5 variants. Immunocytochemical staining revealed that the compound COG5 mutants lead to a significant increase in Golgi fragmentation and DNA damage. Treatment of the transfected cells with PERK inhibitor, GSK2606414, reduced DNA damage levels to that of the control. This study is the first to associate COG5 disruption with ER stress and has identified a potential therapeutic target for patients with COG5-related disorders.
Source: TSpace (University of Toronto)
Author: Sami Tabbarah
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3011343951