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dc.contributor.authorSethna, Saumil
dc.contributor.authorZein, Wadih M
dc.contributor.authorRiaz, Sehar
dc.contributor.authorGiese, Arnaud Pj
dc.contributor.authorSchultz, Julie M
dc.contributor.authorDuncan, Todd
dc.contributor.authorHufnagel, Robert B
dc.contributor.authorBrewer, Carmen C
dc.contributor.authorGriffith, Andrew J
dc.contributor.authorRedmond, T Michael
dc.contributor.authorRiazuddin, Saima
dc.contributor.authorFriedman, Thomas B
dc.contributor.authorAhmed, Zubair M
dc.date.accessioned2021-11-16T13:22:35Z
dc.date.available2021-11-16T13:22:35Z
dc.date.issued2021-11-09
dc.identifier.urihttp://hdl.handle.net/10713/17126
dc.description.abstractUsher syndrome type I (USH1) is characterized by deafness, vestibular areflexia, and progressive retinal degeneration. The protein-truncating p.Arg245* founder variant of PCDH15 (USH1F) has an ~2% carrier frequency amongst Ashkenazi Jews accounts for ~60% of their USH1 cases. Here, longitudinal phenotyping in 13 USH1F individuals revealed progressive retinal degeneration, leading to severe vision loss with macular atrophy by the sixth decade. Half of the affected individuals were legally blind by their mid-50s. The mouse Pcdh15R250X variant is equivalent to human p.Arg245*. Homozygous Pcdh15R250X mice also have visual deficits and aberrant light-dependent translocation of the phototransduction cascade proteins, arrestin, and transducin. Retinal pigment epithelium (RPE)-specific retinoid cycle proteins, RPE65 and CRALBP, were also reduced in Pcdh15R250X mice, indicating a dual role for protocadherin-15 in photoreceptors and RPE. Exogenous 9-cis retinal improved ERG amplitudes in Pcdh15R250X mice, suggesting a basis for a clinical trial of FDA-approved retinoids to preserve vision in USH1F patients.en_US
dc.description.urihttps://doi.org/10.7554/eLife.67361en_US
dc.language.isoenen_US
dc.publishereLife Sciences Publicationsen_US
dc.relation.ispartofeLifeen_US
dc.subjectPCDH15en_US
dc.subjectcell biologyen_US
dc.subjectexogenous retinoidsen_US
dc.subjecthumanen_US
dc.subjectmedicineen_US
dc.subjectmouseen_US
dc.subjectnatural historyen_US
dc.subjectretinal degenerationen_US
dc.subjectusher syndromeen_US
dc.titleProposed therapy, developed in a Pcdh15-deficient mouse, for progressive loss of vision in human Usher syndromeen_US
dc.typeArticleen_US
dc.identifier.doi10.7554/eLife.67361
dc.identifier.pmid34751129
dc.source.volume10
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryEngland


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