{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:03:38Z","timestamp":1791875018226,"version":"4.3.4"},"reference-count":20,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T00:00:00Z","timestamp":1720051200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2019YFA0903800"],"award-info":[{"award-number":["2019YFA0903800"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFA0805701"],"award-info":[{"award-number":["2021YFA0805701"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFA0805905"],"award-info":[{"award-number":["2021YFA0805905"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFA1103603"],"award-info":[{"award-number":["2022YFA1103603"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32071456"],"award-info":[{"award-number":["32071456"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82241224"],"award-info":[{"award-number":["82241224"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anim Models and Exp Med"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Pig organ xenotransplantation is a potential solution for the severe organ shortage in clinic, while immunogenic genes need to be eliminated to improve the immune compatibility between humans and pigs. Current knockout strategies are mainly aimed at the genes causing hyperacute immune rejection (HAR) that occurs in the first few hours while adaptive immune reactions orchestrated by CD4 T cell thereafter also cause graft failure, in which process the MHC II molecule plays critical roles.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Thus, we generate a 4\u2010gene (<jats:italic>GGTA1, CMAH, \u03b24GalNT2,<\/jats:italic> and <jats:italic>CIITA<\/jats:italic>) knockout pig by CRISPR\/Cas9 and somatic cell nuclear transfer to compromise HAR and CD4 T cell reactions simultaneously.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We successfully obtained 4KO piglets with deficiency in all alleles of genes, and at cellular and tissue levels. Additionally, the safety of our animals after gene editing was verified by using whole\u2010genome sequencing and karyotyping. Piglets have survived for more than one year in the barrier, and also survived for more than 3\u2009months in the conventional environment, suggesting that the piglets without MHC II can be raised in the barrier and then gradually mated in the conventional environment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>4KO piglets have lower immunogenicity, are safe in genomic level, and are easier to breed than the model with both MHC I and II deletion.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ame2.12461","type":"journal-article","created":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T08:35:25Z","timestamp":1720082125000},"page":"584-590","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Elimination of <scp><i>GGTA1<\/i><\/scp>, <scp><i>CMAH<\/i><\/scp>, <scp><i>\u03b24GalNT2<\/i><\/scp> and <scp><i>CIITA<\/i><\/scp> genes in pigs compromises human versus pig xenogeneic immune reactions"],"prefix":"10.1002","volume":"7","author":[{"given":"Jing","family":"Xu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology Chinese Academy of Sciences  Beijing China"},{"name":"Key Laboratory of Organ Regeneration and Reconstruction Chinese Academy of Sciences  Beijing China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jilong","family":"Ren","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology Chinese Academy of Sciences  Beijing China"},{"name":"Key Laboratory of Organ Regeneration and Reconstruction Chinese Academy of Sciences  Beijing China"},{"name":"Beijing Institute for Stem Cell and Regenerative Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology Chinese Academy of Sciences  Beijing China"},{"name":"Key Laboratory of Organ Regeneration and Reconstruction Chinese Academy of Sciences  Beijing China"},{"name":"Beijing Institute for Stem Cell and Regenerative Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghui","family":"Fang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, The First Hospital Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meina","family":"Ka","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology Chinese Academy of Sciences  Beijing 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