{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:51:02Z","timestamp":1790394662213,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2012,11,12]],"date-time":"2012-11-12T00:00:00Z","timestamp":1352678400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2013,2]]},"abstract":"<jats:p>\n                    Despite the recent availability of gene\u2010specific nucleases, such as zinc\u2010finger nucleases (ZFNs) and transcription activator\u2010like nucleases (TALENs), there is still a need for new tools to modify the genome of different species in an efficient, rapid, and less costly manner. One aim of this study was to apply, for the first time, engineered meganucleases to mutate an endogenous gene in animal zygotes. The second aim was to target the mouse and rat recombination activating gene 1 (\n                    <jats:italic>Rag1<\/jats:italic>\n                    ) to describe, for the first time,\n                    <jats:italic>Rag1<\/jats:italic>\n                    knockout immunodeficient rats. We microinjected a plasmid encoding a meganuclease for\n                    <jats:italic>Rag1<\/jats:italic>\n                    into the pronucleus of mouse and rat zygotes. Mutant animals were detected by PCR sequencing of the targeted sequence. A homozygous RAG1\u2010deficient rat line was generated and immunophenotyped. Meganucleases were efficient, because 3.4 and 0.6% of mouse and rat microinjected zygotes, respectively, generated mutated animals. RAG1\u2010deficient rats showed significantly decreased proportions and numbers of immature and mature T and B lymphocytes and normal NK cells\n                    <jats:italic>vs.<\/jats:italic>\n                    littermate wild\u2010type controls. In summary, we describe the use of engineered meganucleases to inactivate an endogenous gene with efficiencies comparable to those of ZFNs and TALENs. Moreover, we generated an immunodeficient rat line useful for studies in which there is a need for biological parameters to be analyzed in the absence of immune responses.\u2014M\u00e9noret, S., Fontani\u00e8re, S., Jantz, D., Tesson, L., Thinard, R., R\u00e9my, S., Usal, C., Ouisse, L.\u2010H., Fraichard, A., Anegon, A. Generation of\n                    <jats:italic>Rag1<\/jats:italic>\n                    \u2010knockout immunodeficient rats and mice using engineered meganucleases.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    27, 703\u2013711 (2013).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.12-219907","type":"journal-article","created":{"date-parts":[[2012,11,13]],"date-time":"2012-11-13T20:15:12Z","timestamp":1352837712000},"page":"703-711","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["Generation of\n                    <i>Rag1<\/i>\n                    \u2010knockout immunodeficient rats and mice using engineered meganucleases"],"prefix":"10.1096","volume":"27","author":[{"given":"S\u00e9verine","family":"M\u00e9noret","sequence":"first","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) Unit\u00e9 Mixte de Recherche (UMR)1064, Center for Research in Transplantation and Immunology and Platform Transgenic Rats Nantes Infrastructures en Biologie Sante et Agronomie (IBiSA), Centre National de Recherche Scientifique Nantes France"},{"name":"Institut de Transplantation Urologie\u2010N\u00e9phrologie (ITUN), Centre Hospitalier Universitaire (CHU) Nantes Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Fontani\u00e8re","sequence":"additional","affiliation":[{"name":"genOway Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek","family":"Jantz","sequence":"additional","affiliation":[{"name":"Precision Biosciences Durham North Carolina 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(IBiSA), Centre National de Recherche Scientifique Nantes France"},{"name":"Institut de Transplantation Urologie\u2010N\u00e9phrologie (ITUN), Centre Hospitalier Universitaire (CHU) Nantes Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9verine","family":"R\u00e9my","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) Unit\u00e9 Mixte de Recherche (UMR)1064, Center for Research in Transplantation and Immunology and Platform Transgenic Rats Nantes Infrastructures en Biologie Sante et Agronomie (IBiSA), Centre National de Recherche Scientifique Nantes France"},{"name":"Institut de Transplantation Urologie\u2010N\u00e9phrologie (ITUN), Centre Hospitalier Universitaire (CHU) Nantes Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Usal","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) Unit\u00e9 Mixte de Recherche (UMR)1064, Center for Research in Transplantation and Immunology and Platform Transgenic Rats Nantes Infrastructures en Biologie Sante et Agronomie (IBiSA), Centre National de Recherche Scientifique Nantes France"},{"name":"Institut de Transplantation Urologie\u2010N\u00e9phrologie (ITUN), Centre Hospitalier Universitaire (CHU) Nantes Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laure\u2010H\u00e9l\u00e8ne","family":"Ouisse","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) Unit\u00e9 Mixte de Recherche (UMR)1064, Center for Research in Transplantation and Immunology and Platform Transgenic Rats Nantes Infrastructures en Biologie Sante et Agronomie (IBiSA), Centre National de Recherche Scientifique Nantes France"},{"name":"Institut de Transplantation Urologie\u2010N\u00e9phrologie (ITUN), Centre Hospitalier Universitaire (CHU) Nantes Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Fraichard","sequence":"additional","affiliation":[{"name":"genOway Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"Anegon","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) Unit\u00e9 Mixte de Recherche (UMR)1064, Center for Research in Transplantation and Immunology and Platform Transgenic Rats Nantes Infrastructures en Biologie Sante et Agronomie (IBiSA), Centre National de Recherche Scientifique Nantes France"},{"name":"Institut de Transplantation Urologie\u2010N\u00e9phrologie (ITUN), Centre Hospitalier Universitaire (CHU) Nantes Nantes 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