{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:26:20Z","timestamp":1779927980286,"version":"3.53.1"},"reference-count":45,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T00:00:00Z","timestamp":1706832000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific and Technological Resources Coordination Project of Shaanxi Province","award":["2020PT-002"],"award-info":[{"award-number":["2020PT-002"]}]},{"name":"Scientific and Technological Resources Coordination Project of Shaanxi Province","award":["2022PT-43"],"award-info":[{"award-number":["2022PT-43"]}]},{"name":"Scientific and Technological Resources Coordination Project of Shaanxi Province","award":["2023-CX-PT-18"],"award-info":[{"award-number":["2023-CX-PT-18"]}]},{"name":"Scientific and Technological Resources Coordination Project of Shaanxi Province","award":["SYDW_KY (2021)13"],"award-info":[{"award-number":["SYDW_KY (2021)13"]}]},{"name":"Scientific and Technological Resources Coordination Project of Shaanxi Province","award":["CBSKL2022ZZ28"],"award-info":[{"award-number":["CBSKL2022ZZ28"]}]},{"name":"Special Fund for Military Laboratory Animals","award":["2020PT-002"],"award-info":[{"award-number":["2020PT-002"]}]},{"name":"Special Fund for Military Laboratory Animals","award":["2022PT-43"],"award-info":[{"award-number":["2022PT-43"]}]},{"name":"Special Fund for Military Laboratory Animals","award":["2023-CX-PT-18"],"award-info":[{"award-number":["2023-CX-PT-18"]}]},{"name":"Special Fund for Military Laboratory Animals","award":["SYDW_KY (2021)13"],"award-info":[{"award-number":["SYDW_KY (2021)13"]}]},{"name":"Special Fund for Military Laboratory Animals","award":["CBSKL2022ZZ28"],"award-info":[{"award-number":["CBSKL2022ZZ28"]}]},{"name":"State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers","award":["2020PT-002"],"award-info":[{"award-number":["2020PT-002"]}]},{"name":"State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers","award":["2022PT-43"],"award-info":[{"award-number":["2022PT-43"]}]},{"name":"State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers","award":["2023-CX-PT-18"],"award-info":[{"award-number":["2023-CX-PT-18"]}]},{"name":"State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers","award":["SYDW_KY (2021)13"],"award-info":[{"award-number":["SYDW_KY (2021)13"]}]},{"name":"State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers","award":["CBSKL2022ZZ28"],"award-info":[{"award-number":["CBSKL2022ZZ28"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Severe combined immunodeficient (SCID) mice serve as a critical model for human xenotransplantation studies, yet they often suffer from low engraftment rates and susceptibility to graft-versus-host disease (GVHD). Moreover, certain SCID strains demonstrate \u2018immune leakage\u2019, underscoring the need for novel model development. Here, we introduce an SCID mouse model with a targeted disruption of the dclre1c gene, encoding Artemis, which is essential for V(D)J recombination and DNA repair during T cell receptor (TCR) and B cell receptor (BCR) assembly. Artemis deficiency precipitates a profound immunodeficiency syndrome, marked by radiosensitivity and compromised T and B lymphocyte functionality. Utilizing CRISPR\/Cas9-mediated gene editing, we generated dclre1c-deficient mice with an NOD genetic background. These mice exhibited a radiosensitive SCID phenotype, with pronounced DNA damage and defective thymic, splenic and lymph node development, culminating in reduced T and B lymphocyte populations. Notably, both cell lines and patient-derived tumor xenografts were successfully engrafted into these mice. Furthermore, the human immune system was effectively rebuilt following peripheral blood mononuclear cells (PBMCs) transplantation. The dclre1c-knockout NOD mice described herein represent a promising addition to the armamentarium of models for xenotransplantation, offering a valuable platform for advancing human immunobiological research.<\/jats:p>","DOI":"10.3390\/biom14020180","type":"journal-article","created":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T09:24:08Z","timestamp":1706865848000},"page":"180","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dclre1c-Mutation-Induced Immunocompromised Mice Are a Novel Model for Human Xenograft Research"],"prefix":"10.3390","volume":"14","author":[{"given":"Yixiao","family":"Bin","sequence":"first","affiliation":[{"name":"Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi\u2019an 710032, China"},{"name":"State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Fourth Military Medical University, Xi\u2019an 710032, China"},{"name":"School of Basic Medical Sciences, Shaanxi University of Chinese Medicine, Xianyang 712046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2235-7214","authenticated-orcid":false,"given":"Sanhua","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Reproductive Medicine Center, Tang Du Hospital, Fourth Military Medical University, Xi\u2019an 710038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruo","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi\u2019an 710032, China"},{"name":"State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haowei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi\u2019an 710032, China"},{"name":"State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Fourth Military Medical University, Xi\u2019an 710032, China"},{"name":"School of Basic Medical Sciences, Shaanxi University of Chinese Medicine, Xianyang 712046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peijuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi\u2019an 710032, China"},{"name":"State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqian","family":"Xin","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi\u2019an 710032, China"},{"name":"State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianjiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi\u2019an 710032, China"},{"name":"State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijiao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi\u2019an 710032, China"},{"name":"State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8913-7115","authenticated-orcid":false,"given":"Ke","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi\u2019an 710032, China"},{"name":"State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuan","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi\u2019an 710032, China"},{"name":"State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuxuan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi\u2019an 710032, China"},{"name":"State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhinan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi\u2019an 710032, China"},{"name":"State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7999-0208","authenticated-orcid":false,"given":"Hai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi\u2019an 710032, China"},{"name":"State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1016\/S1097-2765(02)00755-4","article-title":"Leaky Scid Phenotype Associated with Defective V(D)J Coding End Processing in Artemis-Deficient Mice","volume":"10","author":"Rooney","year":"2002","journal-title":"Mol. 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