{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T00:50:54Z","timestamp":1776559854452,"version":"3.51.2"},"reference-count":35,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Interleukin 2 receptor gamma (IL2RG) knockout (KO) is frequently used to generate X-linked severe combined immunodeficiency (X-SCID) models. Humans and pigs have anatomical and physiological similarities; hence, X-SCID pigs are being actively developed. IL2RG KO X-SCID pigs are typically achieved through somatic cell nuclear transfer using genetically modified somatic cells as nuclear donors. Therefore, we investigated the possibility of generating IL2RG KO pigs through electroporation-mediated zygotic gene editing using CRISPR\/Cas9. First, we designed and selected an efficient guide RNA targeting the porcine IL2RG gene. Subsequently, we obtained one mosaic mutant male piglet carrying a frame-shift mutation (\u221219\u2009bp) in IL2RG without off-target events, after the transfer of gene-edited zygotes. We also confirmed that F1 female pigs successfully inherited the \u221219bp mutation (XKOX). Subsequently, we obtained 30 offspring, including 10 IL2RG-KO male pigs (XKOY), from three F1 XKOX litters. The XKOY pigs showed thymic tissue hypoplasia, and flow cytometry analysis revealed absence of cytotoxic T lymphocytes, helper T, and natural killer cells. Typically, X-linked disorders predominantly affect males. Therefore, female carriers pigs are usually maintained and mated with WT males, generating animal models of the disease. In this study, we successfully generated IL2RG-modified F0 male hemizygous pigs rescued by mosaic genotype via electroporation-mediated zygotic gene editing and subsequently generated IL2RG KO pigs by mating F0 pigs with WT females. Our results demonstrated the feasibility of using zygote electroporation to generate IL2RG-deficient pigs. Furthermore, while obtaining a fertile IL2RG mosaic male pig capable of transmitting the mutation was serendipitous, it presents a potential alternative approach for generating X-linked immunodeficiency models.<\/jats:p>","DOI":"10.1093\/jas\/skaf350","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T13:05:39Z","timestamp":1763125539000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>IL2RG<\/i>\n                    deficient X-SCID pigs generated via electroporation-mediated gene editing using CRISPR\/Cas9"],"prefix":"10.1093","volume":"104","author":[{"given":"Maki","family":"Hirata","sequence":"first","affiliation":[{"name":"College of Coastal Agricultural Science, Guangdong Ocean University , Zhanjiang 524088"},{"name":"Bio-Innovation Research Center, Tokushima University , Tokushima 7793233"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhao","family":"Namula","sequence":"additional","affiliation":[{"name":"College of Coastal Agricultural Science, Guangdong Ocean University , Zhanjiang 524088"},{"name":"Bio-Innovation Research Center, Tokushima University , Tokushima 7793233"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingyi","family":"Lin","sequence":"additional","affiliation":[{"name":"College of Coastal Agricultural Science, Guangdong Ocean University , Zhanjiang 524088"},{"name":"Bio-Innovation Research Center, Tokushima University , Tokushima 7793233"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megumi","family":"Nagahara","sequence":"additional","affiliation":[{"name":"College of Coastal Agricultural Science, Guangdong Ocean University , Zhanjiang 524088"},{"name":"Bio-Innovation Research Center, Tokushima University , Tokushima 7793233"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shangquan","family":"Gan","sequence":"additional","affiliation":[{"name":"College of Coastal Agricultural Science, Guangdong Ocean University , Zhanjiang 524088"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianghong","family":"Ju","sequence":"additional","affiliation":[{"name":"College of Coastal Agricultural Science, Guangdong Ocean University , Zhanjiang 524088"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koki","family":"Takebayashi","sequence":"additional","affiliation":[{"name":"Bio-Innovation Research Center, Tokushima University , Tokushima 7793233"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aya","family":"Nakai","sequence":"additional","affiliation":[{"name":"Bio-Innovation Research Center, Tokushima University , Tokushima 7793233"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manita","family":"Wittayarat","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Science, Prince of Songkla University , Songkhla 90110"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshige","family":"Otoi","sequence":"additional","affiliation":[{"name":"College of Coastal Agricultural Science, Guangdong Ocean University , Zhanjiang 524088"},{"name":"Bio-Innovation Research Center, Tokushima University , Tokushima 7793233"},{"name":"Faculty of Veterinary Science, Chulalongkorn University , Bangkok 10330"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuminori","family":"Tanihara","sequence":"additional","affiliation":[{"name":"College of Coastal Agricultural Science, Guangdong Ocean University , Zhanjiang 524088"},{"name":"Bio-Innovation Research Center, Tokushima University , Tokushima 7793233"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"key":"2026041820365623100_skaf350-B1","doi-asserted-by":"publisher","first-page":"100","DOI":"10.3389\/fimmu.2020.00100","article-title":"Novel engraftment and T cell differentiation of human hematopoietic cells in ART(-\/-)IL2RG(-\/Y) SCID pigs","volume":"11","author":"Boettcher","year":"2020","journal-title":"Front. 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