| First Author | Yamaguchi T | Year | 2021 |
| Journal | Front Immunol | Volume | 12 |
| Pages | 671648 | PubMed ID | 34386001 |
| Mgi Jnum | J:323044 | Mgi Id | MGI:6817731 |
| Doi | 10.3389/fimmu.2021.671648 | Citation | Yamaguchi T, et al. (2021) Generation of Novel Human Red Blood Cell-Bearing Humanized Mouse Models Based on C3-Deficient NOG Mice. Front Immunol 12:671648 |
| abstractText | Despite recent advances in immunodeficient mouse models bearing human red blood cells (hRBCs), the elimination of circulating hRBCs by residual innate immune systems remains a significant challenge. In this study, we evaluated the role of mouse complement C3 in the elimination of circulating hRBCs by developing a novel NOG substrain harboring a truncated version of the murine C3 gene (NOG-C3(DeltaMG2-3)). Genetic C3 deletion prolonged the survival of transfused hRBCs in the circulation. Chemical depletion and functional impairment of mouse macrophages, using clodronate liposomes (Clo-lip) or gadolinium chloride (GdCl3), respectively, further extended the survival of hRBCs in NOG-C3(DeltaMG2-3) mice. Low GdCl3 toxicity allowed the establishment of hRBC-bearing mice, in which hRBCs survived for more than 4 weeks with transfusion once a week. In addition, erythropoiesis of human hematopoietic stem cells (hHSCs) was possible in NOG-C3(DeltaMG2-3)/human GM-CSF-IL-3 transgenic mice with Clo-lip treatment. These findings indicate that mouse models harboring hRBCs can be achieved using NOG-C3(DeltaMG2-3) mice, which could facilitate studies of human diseases associated with RBCs. |
