{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T07:34:51Z","timestamp":1781854491456,"version":"3.54.5"},"reference-count":69,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T00:00:00Z","timestamp":1625443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Stichting Uitzicht including the Stichting MD Nederland, Landelijke Stichting voor Blinden en Slechtzienden, Stichting Retina Fonds Nederland, Oogfonds","award":["UZ 2016 - 21"],"award-info":[{"award-number":["UZ 2016 - 21"]}]},{"DOI":"10.13039\/501100010372","name":"Rotterdamse Stichting Blindenbelangen","doi-asserted-by":"publisher","award":["B20160043"],"award-info":[{"award-number":["B20160043"]}],"id":[{"id":"10.13039\/501100010372","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010374","name":"Stichting Blindenhulp","doi-asserted-by":"publisher","award":["*"],"award-info":[{"award-number":["*"]}],"id":[{"id":"10.13039\/501100010374","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010331","name":"Stichting voor Ooglijders","doi-asserted-by":"publisher","award":["*"],"award-info":[{"award-number":["*"]}],"id":[{"id":"10.13039\/501100010331","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010328","name":"Stichting Lijf en Leven","doi-asserted-by":"publisher","award":["42"],"award-info":[{"award-number":["42"]}],"id":[{"id":"10.13039\/501100010328","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Purpose: We developed and phenotyped a pigmented knockout rat model for lecithin retinol acyltransferase (LRAT) using CRISPR\/Cas9. The introduced mutation (c.12delA) is based on a patient group harboring a homologous homozygous frameshift mutation in the LRAT gene (c.12delC), causing a dysfunctional visual (retinoid) cycle. Methods: The introduced mutation was confirmed by DNA and RNA sequencing. The expression of Lrat was determined on both the RNA and protein level in wildtype and knockout animals using RT-PCR and immunohistochemistry. The retinal structure and function, as well as the visual behavior of the Lrat\u2212\/\u2212 and control rats, were characterized using scanning laser ophthalmoscopy (SLO), optical coherence tomography (OCT), electroretinography (ERG) and vision-based behavioral assays. Results: Wildtype animals had high Lrat mRNA expression in multiple tissues, including the eye and liver. In contrast, hardly any expression was detected in Lrat\u2212\/\u2212 animals. LRAT protein was abundantly present in wildtype animals and absent in Lrat\u2212\/\u2212 animals. Lrat\u2212\/\u2212 animals showed progressively reduced ERG potentials compared to wildtype controls from two weeks of age onwards. Vison-based behavioral assays confirmed reduced vision. Structural abnormalities, such as overall retinal thinning, were observed in Lrat\u2212\/\u2212 animals. The retinal thickness in knockout rats was decreased to roughly 80% by four months of age. No functional or structural differences were observed between wildtype and heterozygote animals. Conclusions: Our Lrat\u2212\/\u2212 rat is a new animal model for retinal dystrophy, especially for the LRAT-subtype of early-onset retinal dystrophies. This model has advantages over the existing mouse models and the RCS rat strain and can be used for translational studies of retinal dystrophies.<\/jats:p>","DOI":"10.3390\/ijms22137234","type":"journal-article","created":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T02:59:47Z","timestamp":1625540387000},"page":"7234","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The Lrat\u2212\/\u2212 Rat: CRISPR\/Cas9 Construction and Phenotyping of a New Animal Model for Retinitis Pigmentosa"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0936-3970","authenticated-orcid":false,"given":"C\u00e9line","family":"Koster","sequence":"first","affiliation":[{"name":"Department of Human Genetics Amsterdam, Section of Ophthalmogenetics, Amsterdam University Medical Centers (AUMC), University of Amsterdam (UvA), Location Meibergdreef, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koen","family":"van den Hurk","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Amsterdam, Section of Ophthalmogenetics, Amsterdam University Medical Centers (AUMC), University of Amsterdam (UvA), Location Meibergdreef, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4424-2533","authenticated-orcid":false,"given":"Colby","family":"Lewallen","sequence":"additional","affiliation":[{"name":"Georgia Institute of Technology, G.W. Woodruff School of Mechanical Engineering, Atlanta, GA 30313, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mays","family":"Talib","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7884-0067","authenticated-orcid":false,"given":"Jacoline","family":"ten Brink","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Amsterdam, Section of Ophthalmogenetics, Amsterdam University Medical Centers (AUMC), University of Amsterdam (UvA), Location Meibergdreef, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camiel","family":"Boon","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"},{"name":"Department of Ophthalmology, Amsterdam University Medical Centers (AUMC), University of Amsterdam (UvA), Location Meibergdreef, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6333-9576","authenticated-orcid":false,"given":"Arthur","family":"Bergen","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Amsterdam, Section of Ophthalmogenetics, Amsterdam University Medical Centers (AUMC), University of Amsterdam (UvA), Location Meibergdreef, 1105 AZ Amsterdam, The Netherlands"},{"name":"Department of Ophthalmology, Amsterdam University Medical Centers (AUMC), University of Amsterdam (UvA), Location Meibergdreef, 1105 AZ Amsterdam, The Netherlands"},{"name":"The Netherlands Institute for Neuroscience (NIN-KNAW), 1105 BA Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4489","DOI":"10.1021\/acs.biochem.7b00451","article-title":"Impact of LCA-Associated E14L LRAT Mutation on Protein Stability and Retinoid Homeostasis","volume":"56","author":"Chelstowska","year":"2017","journal-title":"Biochemistry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5690","DOI":"10.1167\/iovs.07-0610","article-title":"Identification of novel mutations in patients with Leber congenital amaurosis and juvenile RP by genome-wide homozygosity mapping with SNP microarrays","volume":"48","author":"Lopez","year":"2007","journal-title":"Investig. 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