{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T23:22:03Z","timestamp":1790896923635,"version":"4.1.0"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2022,8,12]],"date-time":"2022-08-12T00:00:00Z","timestamp":1660262400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Immunodeficient animals are valuable models for the engraftment of exogenous tissues; they are widely used in many fields, including the creation of humanized animal models, as well as regenerative medicine and oncology. Compared with mice, laboratory rats have a larger body size and can more easily undergo transplantation of various tissues and organs. Considering the absence of high-quality resources of immunodeficient rats, we used the CRISPR\/Cas9 genome editing system to knock out the interleukin-2 receptor gamma chain gene (<jats:italic>Il2rg<\/jats:italic>) in F344\/Jcl rats\u2014alone or together with recombination activating gene 2 (<jats:italic>Rag2<\/jats:italic>)\u2014to create a high-quality bioresource that researchers can freely use: severe combined immunodeficiency (SCID) rats. We selected one founder rat with frame-shift mutations in both <jats:italic>Il2rg<\/jats:italic> (5-bp del) and <jats:italic>Rag2<\/jats:italic> ([1-bp del+2-bp ins]\/[7-bp del+2-bp ins]), then conducted mating to establish a line of immunodeficient rats. The immunodeficiency phenotype was preliminarily confirmed by the presence of severe thymic hypoplasia in <jats:italic>Il2rg<\/jats:italic>-single knockout (sKO) and <jats:italic>Il2rg<\/jats:italic>\/<jats:italic>Rag2<\/jats:italic>-double knockout (dKO) rats. Assessment of blood cell counts in peripheral blood showed that the white blood cell count was significantly decreased in sKO and dKO rats, while the red blood cell count was unaffected. The decrease in white blood cell count was mainly caused by a decrease in lymphocytes. Furthermore, analyses of lymphocyte populations via flow cytometry showed that the numbers of B cells (CD3<jats:sup>-<\/jats:sup> CD45<jats:sup>+<\/jats:sup>) and natural killer cells (CD3<jats:sup>-<\/jats:sup> CD161<jats:sup>+<\/jats:sup>) were markedly reduced in both knockout rats. In contrast, T cells were markedly reduced but showed slightly different results between sKO and dKO rats. Notably, our immunodeficient rats do not exhibit growth retardation or gametogenesis defects. This high-quality SCID rat resource is now managed by the National BioResource Project in Japan. Our SCID rat model has been used in various research fields, demonstrating its importance as a bioresource.<\/jats:p>","DOI":"10.1371\/journal.pone.0272950","type":"journal-article","created":{"date-parts":[[2022,8,12]],"date-time":"2022-08-12T17:35:37Z","timestamp":1660325737000},"page":"e0272950","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":23,"title":["A high-quality severe combined immunodeficiency (SCID) rat bioresource"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4020-9290","authenticated-orcid":true,"given":"Yoshiki","family":"Miyasaka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Hattori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Yamauchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miho","family":"Hoshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuto","family":"Yoshimi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeko","family":"Ishida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7543-7301","authenticated-orcid":true,"given":"Tomoji","family":"Mashimo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,8,12]]},"reference":[{"key":"pone.0272950.ref001","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1096\/fj.201800102RR","article-title":"A novel immunodeficient rat model supports human lung cancer xenografts","volume":"33","author":"D He","year":"2019","journal-title":"FASEB J"},{"key":"pone.0272950.ref002","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/nri2017","article-title":"Humanized mice in translational biomedical research","volume":"7","author":"LD Shultz","year":"2007","journal-title":"Nat Rev Immunol"},{"key":"pone.0272950.ref003","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/0092-8674(95)90360-7","article-title":"Defective DNA-dependent protein kinase activity is linked to V (D) J recombination and DNA repair defects associated with the murine scid mutation","volume":"80","author":"T Blunt","year":"1995","journal-title":"Cell"},{"key":"pone.0272950.ref004","doi-asserted-by":"crossref","first-page":"3175","DOI":"10.1182\/blood-2001-12-0207","article-title":"NOD\/SCID\/\u03b3 c null mouse: an excellent recipient mouse model for engraftment of human cells","volume":"100","author":"M Ito","year":"2002","journal-title":"Blood"},{"key":"pone.0272950.ref005","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1111\/j.1365-2249.2008.03753.x","article-title":"Non-obese diabetic\u2013recombination activating gene-1 (NOD\u2013Rag 1 null) interleukin (IL)-2 receptor common gamma chain (IL2r\u03b3 null) null mice: a radioresistant model for human lymphohaematopoietic engraftment","volume":"154","author":"T Pearson","year":"2008","journal-title":"Clin Exp Immunol"},{"key":"pone.0272950.ref006","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.imbio.2018.09.002","article-title":"Are rats more human than mice?","volume":"224","author":"G. 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