{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:39:32Z","timestamp":1790642372905,"version":"4.1.0"},"reference-count":58,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,8,25]],"date-time":"2021-08-25T00:00:00Z","timestamp":1629849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001116","name":"Foundation Fighting Blindness","doi-asserted-by":"publisher","award":["PPA-0517-0717-RAD"],"award-info":[{"award-number":["PPA-0517-0717-RAD"]}],"id":[{"id":"10.13039\/100001116","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SPP2127: NA 1398\/1-1"],"award-info":[{"award-number":["SPP2127: NA 1398\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Retinitis pigmentosa (RP) is an inherited retinal disease (IRD) with an overall prevalence of 1 in 4000 individuals. Mutations in EYS (Eyes shut homolog) are among the most frequent causes of non-syndromic autosomal recessively inherited RP and act via a loss-of-function mechanism. In light of the recent successes for other IRDs, we investigated the therapeutic potential of exon skipping for EYS-associated RP. CRISPR\/Cas9 was employed to generate zebrafish from which the region encompassing the orthologous exons 37-41 of human EYS (eys exons 40-44) was excised from the genome. The excision of these exons was predicted to maintain the open reading frame and to result in the removal of exactly one Laminin G and two EGF domains. Although the eys\u0394exon40-44 transcript was found at levels comparable to wild-type eys, and no unwanted off-target modifications were identified within the eys coding sequence after single-molecule sequencing, Eys\u0394exon40-44 protein expression could not be detected. Visual motor response experiments revealed that eys\u0394exon40-44 larvae were visually impaired and histological analysis revealed a progressive degeneration of the retinal outer nuclear layer in these zebrafish. Altogether, the data obtained in our zebrafish model currently provide no indications for the skipping of EYS exons 37-41 as an effective future treatment strategy for EYS-associated RP.<\/jats:p>","DOI":"10.3390\/ijms22179154","type":"journal-article","created":{"date-parts":[[2021,8,25]],"date-time":"2021-08-25T04:24:27Z","timestamp":1629865467000},"page":"9154","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Zebrafish as a Model to Evaluate a CRISPR\/Cas9-Based Exon Excision Approach as a Future Treatment Option for EYS-Associated Retinitis Pigmentosa"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3575-1301","authenticated-orcid":false,"given":"Renske","family":"Schellens","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"},{"name":"Donders Institute for Brain Cognition and Behaviour, 6500 GL Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3448-3269","authenticated-orcid":false,"given":"Erik","family":"de Vrieze","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"},{"name":"Donders Institute for Brain Cognition and Behaviour, 6500 GL Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pam","family":"Graave","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanne","family":"Broekman","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Nagel-Wolfrum","sequence":"additional","affiliation":[{"name":"Institute for Molecular Physiology, Johannes Gutenberg-University Mainz, 55099 Mainz, Germany"},{"name":"Institute for Developmental Biology and Neurobiology, Johannes Gutenberg-University Mainz, 55099 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theo","family":"Peters","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0841-8693","authenticated-orcid":false,"given":"Hannie","family":"Kremer","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"},{"name":"Donders Institute for Brain Cognition and Behaviour, 6500 GL Nijmegen, The Netherlands"},{"name":"Department of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4347-6503","authenticated-orcid":false,"given":"Rob W. J.","family":"Collin","sequence":"additional","affiliation":[{"name":"Donders Institute for Brain Cognition and Behaviour, 6500 GL Nijmegen, The Netherlands"},{"name":"Department of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5702-3460","authenticated-orcid":false,"given":"Erwin","family":"van Wijk","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"},{"name":"Donders Institute for Brain Cognition and Behaviour, 6500 GL Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.preteyeres.2018.03.005","article-title":"Non-syndromic retinitis pigmentosa","volume":"66","author":"Verbakel","year":"2018","journal-title":"Prog. 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