{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:21:15Z","timestamp":1791976875276,"version":"4.4.0"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,12,27]],"date-time":"2024-12-27T00:00:00Z","timestamp":1735257600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,12,27]],"date-time":"2024-12-27T00:00:00Z","timestamp":1735257600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["2020R1A2C2013101"],"award-info":[{"award-number":["2020R1A2C2013101"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Lab Anim Res"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Genetically immunodeficient mice lacking <jats:italic>Il2rg<\/jats:italic> and <jats:italic>Rag2<\/jats:italic> genes have been widely utilized in the field of biomedical research. However, immunodeficient rats, which offer the advantage of larger size, have not been as extensively used to date. Recently, Severe Combined Immunodeficiency (SCID) rats were generated using CRISPR\/Cas9 system, targeting <jats:italic>Il2rg<\/jats:italic> and <jats:italic>Rag2<\/jats:italic> in National BioResource Project in Japan. We imported and investigated more detailed phenotypes of wild-type (WT) <jats:italic>Il2rg<\/jats:italic> knockout (KO)<jats:italic>, Rag2<\/jats:italic> KO and <jats:italic>Il2rg<\/jats:italic>\/<jats:italic>Rag2<\/jats:italic> KO rats for 20\u00a0weeks.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>During experiments, <jats:italic>Il2rg<\/jats:italic> KO<jats:italic>, Rag2<\/jats:italic> KO and <jats:italic>Il2rg<\/jats:italic>\/<jats:italic>Rag2<\/jats:italic> KO rats showed decreased white blood cells and systemic lymphopenia, with reduced CD4+, CD8+\u2009T cells and CD161+\u2009NK cells. Additionally, all KO strains exhibited reduced relative spleen weights, hypoplasia of the germinal center in the white pulp, and atrophy with the disappearance of the boundary between the cortex and medulla in the thymus, compared to WT rats. Furthermore, we established human acute lymphoblastic leukemia xenograft rat model by intravenously injecting 5.0\u2009\u00d7\u200910<jats:sup>6<\/jats:sup> cells\/kg of NALM6 cells into <jats:italic>Il2rg\/Rag2<\/jats:italic> KO rats.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>These findings indicate that <jats:italic>Il2rg<\/jats:italic> KO, <jats:italic>Rag2<\/jats:italic> KO, and <jats:italic>Il2rg\/Rag2<\/jats:italic> KO rats exhibited SCID phenotypes, suggesting their potential application as immunodeficient animal models for tumor xenograft studies.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s42826-024-00231-5","type":"journal-article","created":{"date-parts":[[2024,12,27]],"date-time":"2024-12-27T06:25:51Z","timestamp":1735280751000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Immune deficiency phenotypes of Il2rg, Rag2 or Il2rg\/Rag2 double knockout rats; establishment of human leukemia xenograft models"],"prefix":"10.1186","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1425-3460","authenticated-orcid":false,"given":"Joo-Il","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun-Jin","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Euna","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoji","family":"Mashimo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9485-516X","authenticated-orcid":false,"given":"Byeong-Cheol","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,27]]},"reference":[{"issue":"1","key":"231_CR1","doi-asserted-by":"publisher","first-page":"79","DOI":"10.2174\/1874226200902010079","volume":"2","author":"JE Beliz\u00e1rio","year":"2009","unstructured":"Beliz\u00e1rio JE. 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This study did not involve human participants or clinical trials, and thus, ethical approval and consent to participate were not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"43"}}