ArticleThe American journal of pathology2017
A Dominant Mutation in Rpe65, D477G, Delays Dark Adaptation and Disturbs the Visual Cycle in the Mutant Knock-In Mice.
Article in The American journal of pathology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 27 citations in OpenAlex.
- Outer retinal tubulation associated with photoreceptor degeneration.Progress in retinal and eye research · 2026Review
- Dynamic Inner Blood Retina Barrier Disruption in Retinitis Pigmentosa.Investigative ophthalmology & visual science · 2025Article
- RPE65 Variant p.(E519K) Causes a Novel Dominant Adult-Onset Maculopathy in 83 Affected Individuals.Investigative ophthalmology & visual science · 2025Article
- Perimacular Atrophy Following Voretigene Neparvovec-Rzyl Treatment in the Setting of Previous Contralateral Eye Treatment With a Different Viral Vector.Translational vision science & technology · 2024Article
- DHA Shortage Causes the Early Degeneration of Photoreceptors and RPE in Mice With Peroxisomal β-Oxidation Deficiency.Investigative ophthalmology & visual science · 2023Article
- Gene Supplementation in Mice Heterozygous for the D477G RPE65 Variant Implicated in Autosomal Dominant Retinitis Pigmentosa.Human gene therapy · 2023Article
- Environmental Light Has an Essential Effect on the Disease Expression in a Dominant RPE65 Mutation.Advances in experimental medicine and biology · 2023Article
- The First Homozygote Mutation c.499G>T (Asp167Tyr) in the RPE65 Gene Encoding Retinoid Isomerohydrolase Causing Retinal DystrophyCurrent issues in molecular biology · 2022Article
- Retinal pigment epithelium 65 kDa protein (RPE65): An update.Progress in retinal and eye research · 2022Review
- The interplay of environmental luminance and genetics in the retinal dystrophy induced by the dominant RPE65 mutation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- A novel phenotype in a family with autosomal dominant retinal dystrophy due to c.1430A > G in retinoid isomerohydrolase (RPE65) and c.37C > T in bestrophin 1 (BEST1).Documenta ophthalmologica. Advances in ophthalmology · 2021Article
- Molecular genetics of inherited retinal degenerations in Icelandic patients.Clinical genetics · 2021Article
- Clinical Perspective: Treating RPE65-Associated Retinal Dystrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- Review
- Phenotypic expansion of autosomal dominant retinitis pigmentosa associated with the D477G mutation inCold Spring Harbor molecular case studies · 2020Article
- Advanced late-onset retinitis pigmentosa with dominant-acting D477G RPE65 mutation is responsive to oral synthetic retinoid therapy.BMJ open ophthalmology · 2020Article
- Investigation and Restoration of BEST1 Activity in Patient-derived RPEs with Dominant Mutations.Scientific reports · 2019Article
- Aberrant RNA splicing is the major pathogenic effect in a knock-in mouse model of the dominantly inherited c.1430A>G human RPE65 mutation.Human mutation · 2019Article
- Generation and Characterization of Induced Pluripotent Stem Cells and Retinal Organoids From a Leber's Congenital Amaurosis Patient With NovelFrontiers in molecular neuroscience · 2019Article
- Two-year progression analysis of RPE65 autosomal dominant retinitis pigmentosa.Ophthalmic genetics · 2018Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
RPE65 is an indispensable component of the retinoid visual cycle in vertebrates, through which the visual chromophore 11-cis-retinal (11-cis-RAL) is generated to maintain normal vision. Various blinding conditions in humans, such as Leber congenital amaurosis and retinitis pigmentosa (RP), are attributed to either homozygous or compound heterozygous mutations in RPE65. Herein, we investigated D477G missense mutation, an unprecedented dominant-acting mutation of RPE65 identified in patients with autosomal dominant RP. We generated a D477G knock-in (KI) mouse and characterized its phenotypes. Although RPE65 protein levels were decreased in heterozygous KI mice, their scotopic, maximal, and photopic electroretinography responses were comparable to those of wild-type (WT) mice in stationary condition. As shown by high-performance liquid chromatography analysis, levels of 11-cis-RAL in fully dark-adapted heterozygous KI mice were similar to that in WT mice. However, kinetics of 11-cis-RAL regeneration after light exposure were significantly slower in heterozygous KI mice compared with WT and RPE65 heterozygous knockout mice. Furthermore, heterozygous KI mice exhibited lower A-wave recovery compared with WT mice after photobleaching, suggesting a delayed dark adaptation. Taken together, these observations suggest that D477G acts as a dominant-negative mutant of RPE65 that delays chromophore regeneration. The KI mice provide a useful model for further understanding of the pathogenesis of RP associated with this RPE65 mutant and for the development of therapeutic strategies.
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