Generation of Novel Human Red Blood Cell-Bearing Humanized Mouse Models Based on C3-Deficient NOG Mice.

ABSTRACT: 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^ΔMG2-3). 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^ΔMG2-3 mice. Low GdCl₃ toxicity allowed the establishment of hRBC-bearin

SUBMITTER: Yamaguchi T 

PROVIDER: S-EPMC8353390 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature