| First Author | Aísa-Marín I | Year | 2020 |
| Journal | Neurobiol Dis | Volume | 146 |
| Pages | 105122 | PubMed ID | 33007388 |
| Mgi Jnum | J:305147 | Mgi Id | MGI:6503613 |
| Doi | 10.1016/j.nbd.2020.105122 | Citation | Aisa-Marin I, et al. (2020) Nr2e3 functional domain ablation by CRISPR-Cas9D10A identifies a new isoform and generates retinitis pigmentosa and enhanced S-cone syndrome models. Neurobiol Dis 146:105122 |
| abstractText | 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 Delta27 is an in-frame deletion of 27bp that ablates the dimerization domain H10, whereas allele DeltaE8 (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 Delta27 mutant shows developmental alterations and a non-progressive electrophysiological dysfunction that resembles the ESCS phenotype. The DeltaE8 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. |
