{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:40:44Z","timestamp":1747186844760,"version":"3.40.5"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T00:00:00Z","timestamp":1673481600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Although human hepatocyte\u2010transplanted immunodeficient mice support infection with hepatitis viruses, these mice fail to develop viral hepatitis due to the lack of an adaptive immune system. In this study, we generated new immunodeficiency cDNA\u2010urokinase\u2010type plasminogen activator (uPA)\/SCID\/Rag2<jats:sup>\u2212\/\u2212<\/jats:sup>\/Jak3<jats:sup>\u2212\/\u2212<\/jats:sup> mice and established a mouse model with both a humanized liver and immune system. Transplantation of human hepatocytes with human leukocyte antigen (HLA)\u2010A24 resulted in establishment of a highly replaced liver in cDNA\u2010uPA\/SCID\/Rag2<jats:sup>\u2212\/\u2212<\/jats:sup>\/Jak3<jats:sup>\u2212\/\u2212<\/jats:sup> mice. These mice were successfully infected with hepatitis B virus (HBV) and hepatitis C virus (HCV) for a prolonged period and facilitate analysis of the effect of anti\u2010HCV drugs. Administration of peripheral blood mononuclear cells (PBMCs) obtained from an HLA\u2010A24 donor resulted in establishment of 22.6%\u201381.3% human CD45\u2010positive mononuclear cell chimerism in liver\u2010infiltrating cells without causing graft\u2010versus\u2010host disease in cDNA\u2010uPA\/SCID\/Rag2<jats:sup>\u2212\/\u2212<\/jats:sup>\/Jak3<jats:sup>\u2212\/\u2212<\/jats:sup> mice without human hepatocyte transplantation. When mice were transplanted with human hepatocytes and then administered HLA\u2010A24\u2010positive human PBMCs, an alloimmune response between transplanted human hepatocytes and PBMCs occurred, with production of transplanted hepatocyte\u2010specific anti\u2010HLA antibody. In conclusion, we succeeded in establishing a humanized liver\/immune system characterized by an allo\u2010reaction between transplanted human immune cells and human liver using a novel cDNA\u2010uPA\/SCID\/Rag2<jats:sup>\u2212\/\u2212<\/jats:sup>\/Jak3<jats:sup>\u2212\/\u2212<\/jats:sup> mouse. This mouse model can be used to generate a chronic hepatitis mouse model with a human immune system with application not only to hepatitis virus virology but also to investigation of the pathology of post\u2010transplantation liver rejection.<\/jats:p>","DOI":"10.1111\/jvh.13793","type":"journal-article","created":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T07:14:16Z","timestamp":1672211656000},"page":"262-272","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A novel cDNA\u2010uPA\/SCID\/Rag2<sup>\u2212\/\u2212<\/sup>\/Jak3<sup>\u2212\/\u2212<\/sup> mouse model for hepatitis virus infection and reconstruction of human immune system"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6002-5213","authenticated-orcid":false,"given":"Takuro","family":"Uchida","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Graduate School of Biomedical and Health Sciences Hiroshima University  Hiroshima Japan"},{"name":"Research Center for Hepatology and Gastroenterology, Graduate School of Biomedical and Health Science Hiroshima University  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuji","family":"Teraoka","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Graduate School of Biomedical and Health Sciences Hiroshima University  Hiroshima Japan"},{"name":"Research Center for Hepatology and Gastroenterology, Graduate School of Biomedical and Health Science Hiroshima University  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0745-991X","authenticated-orcid":false,"given":"Michio","family":"Imamura","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Graduate School of Biomedical and Health Sciences Hiroshima University  Hiroshima Japan"},{"name":"Research Center for Hepatology and Gastroenterology, Graduate School of Biomedical and Health Science Hiroshima University  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiromi","family":"Abe\u2010Chayama","sequence":"additional","affiliation":[{"name":"Research Center for Hepatology and Gastroenterology, Graduate School of Biomedical and Health Science Hiroshima University  Hiroshima Japan"},{"name":"Center for Medical Specialist Graduate Education and Research, Institute of Biomedical and Health Sciences Hiroshima University  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grace Naswa","family":"Makokha","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Graduate School of Biomedical and Health Sciences Hiroshima University  Hiroshima Japan"},{"name":"Research Center for Hepatology and Gastroenterology, Graduate School of Biomedical and Health Science Hiroshima University  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clair Nelson","family":"Hayes","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Graduate School of Biomedical and Health Sciences Hiroshima University  Hiroshima Japan"},{"name":"Research Center for Hepatology and Gastroenterology, Graduate School of Biomedical and Health Science Hiroshima University  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3409-2156","authenticated-orcid":false,"given":"Hiroshi","family":"Aikata","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Graduate School of Biomedical and Health Sciences Hiroshima University  Hiroshima Japan"},{"name":"Research Center for Hepatology and Gastroenterology, Graduate School of Biomedical and Health Science Hiroshima University  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoko","family":"Hamamura","sequence":"additional","affiliation":[{"name":"Research Center for Hepatology and Gastroenterology, Graduate School of Biomedical and Health Science Hiroshima University  Hiroshima Japan"},{"name":"PhoenixBio Co., Ltd.  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