Improved engraftment of human peripheral blood mononuclear cells in NOG MHC double knockout mice generated using CRISPR/Cas9
| Autor: | Riichi Takahashi, Jochen Welcker, Yuyo Ka, Kayo Tomiyama, Misa Mochizuki, Ryoji Ito, Taichi Yamamoto, Tomoyuki Ogura, Motohito Goto, Mamoru Ito, Kenji Kawai, Ikumi Katano, Eiko Nishinaka |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cell Transplantation Immunology Graft vs Host Disease Nod Biology Major histocompatibility complex Severity of Illness Index Peripheral blood mononuclear cell Immunophenotyping Gene Knockout Techniques Mice 03 medical and health sciences 0302 clinical medicine Immune system Mice Inbred NOD In vivo Histocompatibility Antigens Animals Humans Immunology and Allergy CRISPR Gene Editing Mice Knockout Beta-2 microglobulin Graft Survival Immunohistochemistry 030104 developmental biology Genetic Loci Gene Targeting Models Animal Humanized mouse Leukocytes Mononuclear biology.protein CRISPR-Cas Systems Biomarkers Spleen Interleukin Receptor Common gamma Subunit 030215 immunology |
| Zdroj: | Immunology Letters. 229:55-61 |
| ISSN: | 0165-2478 |
| Popis: | Humanized mice are widely used to study the human immune system in vivo and develop therapies for various human diseases. Human peripheral blood mononuclear cells (PBMC)-engrafted NOD/Shi-scid IL2rγnull (NOG) mice are useful models for characterization of human T cells. However, the development of graft-versus-host disease (GVHD) limits the use of NOG PBMC models. We previously established a NOG-major histocompatibility complex class I/II double knockout (dKO) mouse model. Although humanized dKO mice do not develop severe GVHD, they have impaired reproductive performance and reduced chimerism of human cells. In this study, we established a novel beta-2 microglobulin (B2m) KO mouse model using CRISPR/Cas9. By crossing B2m KO mice with I-Ab KO mice, we established a modified dKO (dKO-em) mouse model. Reproductivity was slightly improved in dKO-em mice, compared with conventional dKO (dKO-tm) mice. dKO-em mice showed no signs of GVHD after the transfer of human PBMCs; they also exhibited high engraftment efficiency. Engrafted human PBMCs survived significantly longer in the peripheral blood and spleens of dKO-em mice, compared with dKO-tm mice. In conclusion, dKO-em mice might constitute a promising PBMC-based humanized mouse model for the development and preclinical testing of novel therapeutics for human diseases. |
| Databáze: | OpenAIRE |
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