Section of Virology, Department of Medicine, Imperial College London, London, UK.
Immunology. 2018 May;154(1):50-61. doi: 10.1111/imm.12906. Epub 2018 Mar 9.
Humanized mice are increasingly appreciated as an incredibly powerful platform for infectious disease research. The often very narrow species tropism of many viral infections, coupled with the sometimes misleading results from preclinical studies in animal models further emphasize the need for more predictive model systems based on human cells rather than surrogates. Humanized mice represent such a model and have been greatly enhanced with regards to their immune system reconstitution as well as immune functionality in the past years, resulting in their recommendation as a preclinical model by the US Food and Drug Administration. This review aims to give a detailed summary of the generation of human peripheral blood lymphocyte-, CD34 haematopoietic stem cell- and bone marrow/liver/thymus-reconstituted mice and available improved models (e.g. myeloid- or T-cell-only mice, MISTRG, NSG-SGM3). Additionally, we summarize human-tropic viral infections, for which humanized mice offer a novel approach for the study of disease pathogenesis as well as future perspectives for their use in biomedical, drug and vaccine research.
人源化小鼠作为一种强大的传染病研究平台，越来越受到重视。许多病毒感染的物种趋向性往往非常狭窄，再加上动物模型的临床前研究有时会得出误导性的结果，这进一步强调了需要基于人类细胞而不是替代物的更具预测性的模型系统。人源化小鼠就是这样一种模型，近年来，它们的免疫系统重建以及免疫功能得到了极大的增强，因此被美国食品和药物管理局推荐作为临床前模型。本文旨在详细总结外周血淋巴细胞、CD34 造血干细胞和骨髓/肝脏/胸腺重建的小鼠以及现有改良模型（如髓样细胞或 T 细胞仅小鼠、MISTRG、NSG-SGM3）的生成。此外，我们还总结了人嗜性病毒感染，对于这些感染，人源化小鼠为研究疾病发病机制提供了一种新方法，并且为其在生物医学、药物和疫苗研究中的应用提供了未来的前景。
