Abstract
An extraneous exon-skipping mRNA encodes an altered form of a light-absorbing opsin in human retina and pigment epithelium (RPE). The predicted protein variant differs from full-length RPE-retinal G protein-coupled receptor (RGR) by having an in-frame deletion of exon 6, which contains the entire sixth transmembrane domain. To verify that the exon 6-deleted RGR protein (RGR-d) exists in human retinas, we have produced RGR-d antibody probes. In Western blot assays, the RGR-d protein was detected in retinas of a large proportion ( approximately 53%) of individual donors, including patients with age-related macular degeneration (AMD). The relative abundance of RGR-d varied significantly between individuals. The altered protein is expressed in RPE cells and has a more basal subcellular localization that is remarkably different from that of normal RGR opsin. The presence of this exon-skipping variant of RGR in humans may contribute to the progressive derangement of the RPE.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Aged
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Aged, 80 and over
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Antibodies / immunology
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Blotting, Western / methods
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Exons / genetics
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Eye Proteins / analysis*
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Eye Proteins / genetics
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Eye Proteins / immunology
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Female
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Gene Deletion
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Humans
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Immunohistochemistry / methods
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Macular Degeneration / genetics
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Macular Degeneration / immunology
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Macular Degeneration / metabolism
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Male
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Middle Aged
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Pigment Epithelium of Eye / chemistry*
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Pigment Epithelium of Eye / immunology
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RNA Splicing / genetics
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RNA, Messenger / genetics
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Receptors, G-Protein-Coupled / analysis*
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Receptors, G-Protein-Coupled / genetics
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Receptors, G-Protein-Coupled / immunology
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Recombinant Proteins / analysis
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Recombinant Proteins / genetics
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Recombinant Proteins / immunology
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Retina / chemistry*
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Retina / immunology
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Rod Opsins / analysis*
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Rod Opsins / genetics
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Rod Opsins / immunology
Substances
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Antibodies
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Eye Proteins
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G protein-coupled receptor RGR
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RNA, Messenger
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Receptors, G-Protein-Coupled
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Recombinant Proteins
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Rod Opsins