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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/172472
Nr2e3 functional domain ablation by CRISPR-Cas9D10A identifies a new isoform and generates retinitis pigmentosa and enhanced S-cone syndrome models
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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.
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AÍSA-MARÍN, Izarbe, et al. Nr2e3 functional domain ablation by CRISPR-Cas9D10A identifies a new isoform and generates retinitis pigmentosa and enhanced S-cone syndrome models. Neurobiology of Disease. 2020. Vol. 146, núm. 105122. ISSN 0969-9961. [consulta: 7 de maig de 2026]. Disponible a: https://hdl.handle.net/2445/172472