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http://hdl.handle.net/2445/172472
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DC Field | Value | Language |
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dc.contributor.author | Aísa-Marín, Izarbe | - |
dc.contributor.author | López-Iniesta, M.José | - |
dc.contributor.author | Milla, Santiago | - |
dc.contributor.author | Lillo, Jaume | - |
dc.contributor.author | Navarro Brugal, Gemma | - |
dc.contributor.author | de la Villa, Pedro | - |
dc.contributor.author | Marfany i Nadal, Gemma | - |
dc.date.accessioned | 2020-11-30T18:10:33Z | - |
dc.date.available | 2021-10-31T06:10:19Z | - |
dc.date.issued | 2020-10 | - |
dc.identifier.issn | 0969-9961 | - |
dc.identifier.uri | http://hdl.handle.net/2445/172472 | - |
dc.description.abstract | Mutations in NR2E3 cause retinitis pigmentosa (RP) and enhanced S-cone syndrome (ESCS) in humans. This gene produces a large isoform encoded in 8 exons and a previously unreported shorter isoform of 7 exons, whose function is unknown. We generated two mouse models by targeting exon 8 of Nr2e3 using CRISPR/Cas9-D10A nickase. Allele Δ27 is an in-frame deletion of 27 bp that ablates the dimerization domain H10, whereas allele ΔE8 (full deletion of exon 8) produces only the short isoform, which lacks the C-terminal part of the ligand binding domain (LBD) that encodes both H10 and the AF2 domain involved in the Nr2e3 repressor activity. The Δ27 mutant shows developmental alterations and a non-progressive electrophysiological dysfunction that resembles the ESCS phenotype. The ΔE8 mutant exhibits progressive retinal degeneration, as occurs in human RP patients. Our mutants suggest a role for Nr2e3 as a cone-patterning regulator and provide valuable models for studying mechanisms of NR2E3-associated retinal dystrophies and evaluating potential therapies. | - |
dc.format.extent | 16 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Elsevier | - |
dc.relation.isformatof | Versió postprint del document publicat a: https://doi.org/10.1016/j.nbd.2020.105122 | - |
dc.relation.ispartof | Neurobiology of Disease, 2020, vol. 146, p. 105122 | - |
dc.relation.uri | https://doi.org/10.1016/j.nbd.2020.105122 | - |
dc.rights | cc-by-nc-nd (c) Elsevier, 2020 | - |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es | - |
dc.source | Articles publicats en revistes (Genètica, Microbiologia i Estadística) | - |
dc.subject.classification | Malalties de la retina | - |
dc.subject.other | Retinal diseases | - |
dc.title | Nr2e3 functional domain ablation by CRISPR-Cas9D10A identifies a new isoform and generates retinitis pigmentosa and enhanced S-cone syndrome models | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/acceptedVersion | - |
dc.identifier.idgrec | 704940 | - |
dc.date.updated | 2020-11-30T18:10:33Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
Appears in Collections: | Articles publicats en revistes (Genètica, Microbiologia i Estadística) |
Files in This Item:
File | Description | Size | Format | |
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704940.pdf | 5.44 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License