{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T10:11:10Z","timestamp":1788343870363,"version":"build-2803163510"},"reference-count":31,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T00:00:00Z","timestamp":1645747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["#"],"award-info":[{"award-number":["#"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013875","name":"Retina France","doi-asserted-by":"publisher","award":["#"],"award-info":[{"award-number":["#"]}],"id":[{"id":"10.13039\/501100013875","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fondation Valentin Hau\u0308y","award":["#"],"award-info":[{"award-number":["#"]}]},{"name":"UNADEV-ITMO-AVIESAN","award":["#"],"award-info":[{"award-number":["#"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Retinitis pigmentosa is an inherited retinal dystrophy that ultimately leads to blindness due to the progressive degeneration of rod photoreceptors and the subsequent non-cell autonomous death of cones. Rhodopsin is the most frequently mutated gene in this disease. We here developed rhodopsin gene editing-based models of retinitis pigmentosa in two Xenopus species, Xenopus laevis and Xenopus tropicalis, by using CRISPR\/Cas9 technology. In both of them, loss of rhodopsin function results in massive rod cell degeneration characterized by progressive shortening of outer segments and occasional cell death. This is followed by cone morphology deterioration. Despite these apparently similar degenerative environments, we found that M\u00fcller glial cells behave differently in Xenopus laevis and Xenopus tropicalis. While a significant proportion of M\u00fcller cells re-enter into the cell cycle in Xenopus laevis, their proliferation remains extremely limited in Xenopus tropicalis. This work thus reveals divergent responses to retinal injury in closely related species. These models should help in the future to deepen our understanding of the mechanisms that have shaped regeneration during evolution, with tremendous differences across vertebrates.<\/jats:p>","DOI":"10.3390\/cells11050807","type":"journal-article","created":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T10:00:40Z","timestamp":1645783240000},"page":"807","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["CRISPR\/Cas9-Mediated Models of Retinitis Pigmentosa Reveal Differential Proliferative Response of M\u00fcller Cells between Xenopus laevis and Xenopus tropicalis"],"prefix":"10.3390","volume":"11","author":[{"given":"Karine","family":"Parain","sequence":"first","affiliation":[{"name":"Paris-Saclay Institute of Neuroscience, CNRS, Universit\u00e9 Paris-Saclay, CERTO-Retina France, 91400 Saclay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Lourdel","sequence":"additional","affiliation":[{"name":"Paris-Saclay Institute of Neuroscience, CNRS, Universit\u00e9 Paris-Saclay, CERTO-Retina France, 91400 Saclay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Donval","sequence":"additional","affiliation":[{"name":"Paris-Saclay Institute of Neuroscience, CNRS, Universit\u00e9 Paris-Saclay, CERTO-Retina France, 91400 Saclay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Chesneau","sequence":"additional","affiliation":[{"name":"Paris-Saclay Institute of Neuroscience, CNRS, Universit\u00e9 Paris-Saclay, CERTO-Retina France, 91400 Saclay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8531-409X","authenticated-orcid":false,"given":"Caroline","family":"Borday","sequence":"additional","affiliation":[{"name":"Paris-Saclay Institute of Neuroscience, CNRS, Universit\u00e9 Paris-Saclay, CERTO-Retina France, 91400 Saclay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odile","family":"Bronchain","sequence":"additional","affiliation":[{"name":"Paris-Saclay Institute of Neuroscience, CNRS, Universit\u00e9 Paris-Saclay, CERTO-Retina France, 91400 Saclay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgane","family":"Locker","sequence":"additional","affiliation":[{"name":"Paris-Saclay Institute of Neuroscience, CNRS, Universit\u00e9 Paris-Saclay, CERTO-Retina France, 91400 Saclay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muriel","family":"Perron","sequence":"additional","affiliation":[{"name":"Paris-Saclay Institute of Neuroscience, CNRS, Universit\u00e9 Paris-Saclay, CERTO-Retina France, 91400 Saclay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.preteyeres.2006.05.003","article-title":"M\u00fcller cells in the healthy and diseased retina","volume":"25","author":"Bringmann","year":"2006","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.gde.2016.05.009","article-title":"Retina regeneration in zebrafish","volume":"40","author":"Wan","year":"2016","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1002\/glia.23165","article-title":"M\u00fcller glial cell reactivation in Xenopus models of retinal degeneration","volume":"65","author":"Langhe","year":"2017","journal-title":"Glia"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Salman, A., McClements, M.E., and MacLaren, R.E. (2021). Insights on the Regeneration Potential of M\u00fcller Glia in the Mammalian Retina. Cells, 10.","DOI":"10.3390\/cells10081957"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.gde.2020.05.025","article-title":"Update on M\u00fcller glia regenerative potential for retinal repair","volume":"64","author":"Locker","year":"2020","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1146\/annurev-vision-121219-081808","article-title":"Reprogramming M\u00fcller Glia to Regenerate Retinal Neurons","volume":"6","author":"Lahne","year":"2020","journal-title":"Annu. Rev. Vis. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.gde.2016.05.028","article-title":"Retinal regeneration in birds and mice","volume":"40","author":"Wilken","year":"2016","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.ydbio.2006.11.024","article-title":"Neural retinal regeneration in the anuran amphibian Xenopus laevis post-metamorphosis: Transdifferentiation of retinal pigmented epithelium regenerates the neural retina","volume":"303","author":"Yoshii","year":"2007","journal-title":"Dev. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1002\/dneu.22169","article-title":"Retinal stem\/progenitor cells in the ciliary marginal zone complete retinal regeneration: A study of retinal regeneration in a novel animal model","volume":"74","author":"Miyake","year":"2014","journal-title":"Dev. Neurobiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.preteyeres.2017.10.002","article-title":"The molecular and cellular basis of rhodopsin retinitis pigmentosa reveals potential strategies for therapy","volume":"62","author":"Athanasiou","year":"2018","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6920","DOI":"10.1038\/s41598-017-07153-4","article-title":"Modeling Dominant and Recessive Forms of Retinitis Pigmentosa by Editing Three Rhodopsin-Encoding Genes in Xenopus Laevis Using Crispr\/Cas9","volume":"7","author":"Feehan","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1242\/dev.099853","article-title":"Efficient RNA\/Cas9-mediated genome editing in Xenopus tropicalis","volume":"141","author":"Guo","year":"2014","journal-title":"Development"},{"key":"ref_13","unstructured":"Nieuwkoop, P., and Faber, J. (1994). Normal Table of Xenopus laevis, Garland Pub."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e168","DOI":"10.1093\/nar\/gku936","article-title":"Easy quantitative assessment of genome editing by sequence trace decomposition","volume":"42","author":"Brinkman","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_15","first-page":"587","article-title":"Targeted disruption of the endogenous zebrafish rhodopsin locus as models of rapid rod photoreceptor degeneration","volume":"24","author":"Zelinka","year":"2018","journal-title":"Mol. Vis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1111\/gtc.12379","article-title":"Rapid and efficient analysis of gene function using CRISPR-Cas9 in Xenopus tropicalis founders","volume":"21","author":"Shigeta","year":"2016","journal-title":"Genes Cells"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-020-70735-2","article-title":"CRISPR\/Cas9 mediated mutation of the mtnr1a melatonin receptor gene causes rod photoreceptor degeneration in developing Xenopus tropicalis","volume":"10","author":"Wiechmann","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.ydbio.2018.10.008","article-title":"Mosaicism in CRISPR\/Cas9-mediated genome editing","volume":"445","author":"Mehravar","year":"2019","journal-title":"Dev. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1002\/(SICI)1097-4695(19980605)35:3<227::AID-NEU1>3.0.CO;2-0","article-title":"Sequential genesis and determination of cone and rod photoreceptors in Xenopus","volume":"35","author":"Chang","year":"1998","journal-title":"J. Neurobiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"33912","DOI":"10.1074\/jbc.M113.483032","article-title":"Retinitis pigmentosa mutants provide insight into the role of the N-terminal cap in rhodopsin folding, structure, and function","volume":"288","author":"Opefi","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1167\/iovs.16-21366","article-title":"Retinal Degeneration Triggers the Activation of YAP\/TEAD in Reactive M\u00fcller Cells","volume":"58","author":"Hamon","year":"2017","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1002\/cne.21746","article-title":"Sox9 is expressed in mouse multipotent retinal progenitor cells and functions in M\u00fcller glial cell development","volume":"510","author":"Furuta","year":"2008","journal-title":"J. Comp. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.ddtec.2018.07.001","article-title":"CRISPR\/Cas9 disease models in zebrafish and Xenopus: The genetic renaissance of fish and frogs","volume":"28","author":"Naert","year":"2018","journal-title":"Drug Discov. Today Technol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/ng0297-216","article-title":"Retinopathy induced in mice by targeted disruption of the rhodopsin gene","volume":"15","author":"Humphries","year":"1997","journal-title":"Nat. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1017\/S0952523801183100","article-title":"Comparative structural and functional analysis of photoreceptor neurons of Rho-\/- mice reveal increased survival on C57BL\/6J in comparison to 129Sv genetic background","volume":"18","author":"Humphries","year":"2001","journal-title":"Vis. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.4103\/1673-5374.147942","article-title":"A novel mode of retinal regeneration: The merit of a new Xenopus model","volume":"9","author":"Araki","year":"2014","journal-title":"Neural Regen. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.exer.2013.07.009","article-title":"The retinal pigment epithelium: An important player of retinal disorders and regeneration","volume":"123","author":"Chiba","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Lust, K., and Wittbrodt, J. (2018). Activating the regenerative potential of M\u00fcller glia cells in a regeneration-deficient retina. Elife, 7.","DOI":"10.7554\/eLife.32319"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.ydbio.2021.01.005","article-title":"Nutrient availability contributes to a graded refractory period for regeneration in Xenopus tropicalis","volume":"473","author":"Williams","year":"2021","journal-title":"Dev. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1002\/dneu.20610","article-title":"Genetic dissection reveals two separate pathways for rod and cone regeneration in the teleost retina","volume":"68","author":"Morris","year":"2008","journal-title":"Dev. Neurobiol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Santhanam, A., Shihabeddin, E., Atkinson, J.A., Nguyen, D., Lin, Y.-P., and O\u2019Brien, J. (2020). A Zebrafish Model of Retinitis Pigmentosa Shows Continuous Degeneration and Regeneration of Rod Photoreceptors. Cells, 9.","DOI":"10.3390\/cells9102242"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/5\/807\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:27:39Z","timestamp":1760135259000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/5\/807"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,25]]},"references-count":31,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["cells11050807"],"URL":"https:\/\/doi.org\/10.3390\/cells11050807","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,25]]}}}