title: Moderate light-induced degeneration of rod photoreceptors with delayed transducin translocation in shaker1 mice.
abstract: PURPOSE. Usher syndrome is characterized by congenital deafness associated with retinitis pigmentosa (RP). Mutations in the myosin VIIa gene (MYO7A) cause a common and severe subtype of Usher syndrome (USH1B). Shaker1 mice have mutant MYO7A. They are deaf and have vestibular dysfunction but do not develop photoreceptor degeneration. The goal of this study was to investigate abnormalities of photoreceptors in shaker1 mice. METHODS. Immunocytochemistry and hydroethidine-based detection of intracellular superoxide production were used. Photoreceptor cell densities under various conditions of light/dark exposures were evaluated. RESULTS. In shaker1 mice, the rod transducin translocation is delayed because of a shift of its light activation threshold to a higher level. Even moderate light exposure can induce oxidative damage and significant rod degeneration in shaker1 mice. Shaker1 mice reared under a moderate light/dark cycle develop severe retinal degeneration in less than 6 months. CONCLUSIONS. These findings show that, contrary to earlier studies, shaker1 mice possess a robust retinal phenotype that may link to defective rod protein translocation. Importantly, USH1B animal models are likely vulnerable to light-induced photoreceptor damage, even under moderate light.
authors: National Usher Syndrome Center, Boys Town National Research Hospital, Omaha, Nebraska, USA. you-wei.peng@boystown.org
authors: You-Wei
authors: YW
authors: Peng
authors: Marisa
authors: M
authors: Zallocchi
authors: Wei-Min
authors: WM
authors: Wang
authors: Duane
authors: D
authors: Delimont
authors: Dominic
authors: D
authors: Cosgrove
mesh_terms: D000818:Animals; D002452:Cell Count; D019084:Fluorescent Antibody Technique, Indirect; D044385:GTP-Binding Protein alpha Subunits / Q000378:metabolism*; D008027:Light / Q000009:adverse effects*; D051379:Mice; D008817:Mice, Mutant Strains; D000081412:Myosin VIIa; D009218:Myosins / Q000235:genetics; D018384:Oxidative Stress; D021381:Protein Transport; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000378:metabolism*; D012162:Retinal Degeneration / Q000209:etiology / Q000378:metabolism*; D017948:Retinal Rod Photoreceptor Cells / Q000528:radiation effects*; D013481:Superoxides / Q000378:metabolism; D015293:Transducin / Q000378:metabolism*; D052245:Usher Syndromes / Q000209:etiology / Q000235:genetics / Q000378:metabolism*
chemical_list: D044385:GTP-Binding Protein alpha Subunits; C488949:Gnat1 protein, mouse; C000631456:Myo7a protein, mouse; D000081412:Myosin VIIa; D013481:Superoxides; D009218:Myosins; D015293:Transducin