Aísa-Marín, IzarbeLópez-Iniesta, M.JoséMilla, SantiagoLillo, JaumeNavarro Brugal, Gemmade la Villa, PedroMarfany i Nadal, Gemma2020-11-302021-10-312020-100969-9961https://hdl.handle.net/2445/172472Mutations 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.16 p.application/pdfengcc-by-nc-nd (c) Elsevier, 2020http://creativecommons.org/licenses/by-nc-nd/3.0/esMalalties de la retinaRetinal diseasesinfo:eu-repo/semantics/article7049402020-11-30info:eu-repo/semantics/openAccess