<i>Dclre1c</i>-Mutation-Induced Immunocompromised Mice Are a Novel Model for Human Xenograft Research
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 ‘immune leakage’, underscoring the need for...
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| Format: | Article |
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MDPI AG
2024-02-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/14/2/180 |
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| author | Yixiao Bin Sanhua Wei Ruo Chen Haowei Zhang Jing Ren Peijuan Liu Zhiqian Xin Tianjiao Zhang Haijiao Yang Ke Wang Zhuan Feng Xiuxuan Sun Zhinan Chen Hai Zhang |
| author_facet | Yixiao Bin Sanhua Wei Ruo Chen Haowei Zhang Jing Ren Peijuan Liu Zhiqian Xin Tianjiao Zhang Haijiao Yang Ke Wang Zhuan Feng Xiuxuan Sun Zhinan Chen Hai Zhang |
| author_sort | Yixiao Bin |
| collection | DOAJ |
| description | 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 ‘immune leakage’, underscoring the need for novel model development. Here, we introduce an SCID mouse model with a targeted disruption of the <i>dclre1c</i> 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 <i>dclre1c</i>-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 <i>dclre1c</i>-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. |
| first_indexed | 2024-03-07T22:41:06Z |
| format | Article |
| id | doaj.art-e7faabe2416a4baf92bcef238975f733 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-07T22:41:06Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-e7faabe2416a4baf92bcef238975f7332024-02-23T15:09:18ZengMDPI AGBiomolecules2218-273X2024-02-0114218010.3390/biom14020180<i>Dclre1c</i>-Mutation-Induced Immunocompromised Mice Are a Novel Model for Human Xenograft ResearchYixiao Bin0Sanhua Wei1Ruo Chen2Haowei Zhang3Jing Ren4Peijuan Liu5Zhiqian Xin6Tianjiao Zhang7Haijiao Yang8Ke Wang9Zhuan Feng10Xiuxuan Sun11Zhinan Chen12Hai Zhang13Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi’an 710032, ChinaDepartment of Obstetrics and Gynecology, Reproductive Medicine Center, Tang Du Hospital, Fourth Military Medical University, Xi’an 710038, ChinaDepartment of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi’an 710032, ChinaDepartment 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’an 710032, ChinaDepartment of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi’an 710032, ChinaDepartment of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi’an 710032, ChinaDepartment of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi’an 710032, ChinaDepartment of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi’an 710032, ChinaDepartment of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi’an 710032, ChinaDepartment of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi’an 710032, ChinaDepartment of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi’an 710032, ChinaDepartment of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi’an 710032, ChinaDepartment of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi’an 710032, ChinaDepartment of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi’an 710032, ChinaSevere 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 ‘immune leakage’, underscoring the need for novel model development. Here, we introduce an SCID mouse model with a targeted disruption of the <i>dclre1c</i> 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 <i>dclre1c</i>-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 <i>dclre1c</i>-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.https://www.mdpi.com/2218-273X/14/2/180<i>dclre1c</i>CRISPR/Cas9knockouttumor xenograft modelimmune reconstitution |
| spellingShingle | Yixiao Bin Sanhua Wei Ruo Chen Haowei Zhang Jing Ren Peijuan Liu Zhiqian Xin Tianjiao Zhang Haijiao Yang Ke Wang Zhuan Feng Xiuxuan Sun Zhinan Chen Hai Zhang <i>Dclre1c</i>-Mutation-Induced Immunocompromised Mice Are a Novel Model for Human Xenograft Research Biomolecules <i>dclre1c</i> CRISPR/Cas9 knockout tumor xenograft model immune reconstitution |
| title | <i>Dclre1c</i>-Mutation-Induced Immunocompromised Mice Are a Novel Model for Human Xenograft Research |
| title_full | <i>Dclre1c</i>-Mutation-Induced Immunocompromised Mice Are a Novel Model for Human Xenograft Research |
| title_fullStr | <i>Dclre1c</i>-Mutation-Induced Immunocompromised Mice Are a Novel Model for Human Xenograft Research |
| title_full_unstemmed | <i>Dclre1c</i>-Mutation-Induced Immunocompromised Mice Are a Novel Model for Human Xenograft Research |
| title_short | <i>Dclre1c</i>-Mutation-Induced Immunocompromised Mice Are a Novel Model for Human Xenograft Research |
| title_sort | i dclre1c i mutation induced immunocompromised mice are a novel model for human xenograft research |
| topic | <i>dclre1c</i> CRISPR/Cas9 knockout tumor xenograft model immune reconstitution |
| url | https://www.mdpi.com/2218-273X/14/2/180 |
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