Phenotypic characterization of P23H and S334ter rhodopsin transgenic rat models of inherited retinal degeneration.

摘要: Abstract We produced 8 lines of transgenic (Tg) rats expressing one two different rhodopsin mutations in albino Sprague-Dawley (SD) rats. Three were generated with a proline to histidine substitution at codon 23 (P23H), the most common autosomal dominant form retinitis pigmentosa United States. Five termination position 334 (S334ter), resulting C-terminal truncated opsin protein lacking last 15 amino acid residues and containing all phosphorylation sites involved deactivation, as well terminal QVAPA important for deactivation trafficking. The rates photoreceptor (PR) degeneration these models vary proportion ratio mutant wild-type rhodopsin. have been widely studied, but many aspects their phenotypes not described. Here we present comprehensive study 8 Tg lines, including time course PR from onset year age, retinal structure by light electron microscopy (EM), hemispheric asymmetry gradients rod cone degeneration, content, gene dosage effect, rapid activation invasion outer retina presumptive microglia, segment disc shedding phagocytosis pigmented epithelium (RPE), function electroretinogram (ERG). biphasic nature cell death was noted, lack an injury-induced protective response rat models. EM analysis revealed accumulation submicron vesicular structures interphotoreceptor space during peak period S334ter lines. This is likely due elimination trafficking consensus domain seen before other mutants QVAPA. Tg been, will continue be, extremely useful experimental inherited degenerations.