ArticleHuman molecular genetics2014
The Y141C knockin mutation in RDS leads to complex phenotypes in the mouse.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 45 citations in OpenAlex.
- Advancing genetic pathogenicity prediction with three-dimensional proteoform-phenotype analysis.medRxiv : the preprint server for health sciences · 2026Article
- Downregulation of rhodopsin is an effective therapeutic strategy in ameliorating peripherin-2-associated inherited retinal disorders.Nature communications · 2024Article
- Article
- Prph2 knock-in mice recapitulate human central areolar choroidal dystrophy retinal degeneration and exhibit aberrant synaptic remodeling and microglial activation.Cell death & disease · 2023Article
- ROM1 is redundant to PRPH2 as a molecular building block of photoreceptor disc rims.bioRxiv : the preprint server for biology · 2023Article
- Comparative study of PRPH2 D2 loop mutants reveals divergent disease mechanism in rods and cones.Cellular and molecular life sciences : CMLS · 2023Article
- Photoreceptor disc incisures form as an adaptive mechanism ensuring the completion of disc enclosure.eLife · 2023Article
- Photoreceptor disc incisures form as an adaptive mechanism ensuring the completion of disc enclosure.bioRxiv : the preprint server for biology · 2023Article
- The usherin mutation c.2299delG leads to its mislocalization and disrupts interactions with whirlin and VLGR1.Nature communications · 2023Article
- Delineating the Clinical Phenotype of Patients With the c.629C>G, p.Pro210Arg Mutation in Peripherin-2.Investigative ophthalmology & visual science · 2022Article
- Prph2 disease mutations lead to structural and functional defects in the RPE.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- The Neuroprotective Role of Retbindin, a Metabolic Regulator in the Neural Retina.Frontiers in pharmacology · 2022Review
- Modulation of SOD3 Levels Is Detrimental to Retinal Homeostasis.Antioxidants (Basel, Switzerland) · 2021Article
- Adherent but Not Suspension-Cultured Embryoid Bodies Develop into Laminated Retinal Organoids.Journal of developmental biology · 2021Article
- Retbindin: A riboflavin Binding Protein, Is Critical for Photoreceptor Homeostasis and Survival in Models of Retinal Degeneration.International journal of molecular sciences · 2020Article
- ROM1 contributes to phenotypic heterogeneity in PRPH2-associated retinal disease.Human molecular genetics · 2020Article
- Syntaxin 3 is essential for photoreceptor outer segment protein trafficking and survival.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Review
- Review
- Pluripotent Stem Cells for the Treatment of Retinal Degeneration: Current Strategies and Future Directions.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in the photoreceptor-specific gene peripherin-2 (PRPH-2, also known as retinal degeneration slow/RDS) cause incurable retinal degeneration with a high degree of phenotypic variability. Patient phenotypes range from retinitis pigmentosa to various forms of macular and pattern dystrophy. Macular and pattern dystrophy in particular are associated with complex, poorly understood disease mechanisms, as severe vision loss is often associated both with defects in the photoreceptors, as well as the choroid and retinal pigment epithelium (RPE). Since there is currently no satisfactory model to study pattern dystrophy disease mechanisms, we generated a knockin mouse model expressing an RDS pattern dystrophy mutation, Y141C. Y141C mice exhibited clinical signs similar to those in patients including late-onset fundus abnormalities characteristic of RPE and choroidal defects and electroretinogram defects. Ultrastructural examination indicated that disc formation was initiated by the Y141C protein, but proper sizing and alignment of discs required wild-type RDS. The biochemical mechanism underlying these abnormalities was tied to defects in the normal process of RDS oligomerization which is required for proper RDS function. Y141C-RDS formed strikingly abnormal disulfide-linked complexes which were localized to the outer segment (OS) where they impaired the formation of proper OS structure. These data support a model of pattern dystrophy wherein a primary molecular defect occurring in all photoreceptors leads to secondary sequellae in adjacent tissues, an outcome which leads to macular vision loss. An understanding of the role of RDS in the interplay between these tissues significantly enhances our understanding of RDS-associated pathobiology and our ability to design rational treatment strategies.
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