Rehermann Barbara, Graham Andrea L, Masopust David, Hamilton Sara E
Immunology Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Department of Ecology & Evolutionary Biology, Princeton University, Princeton, NJ, USA.
Nat Rev Immunol. 2025 May;25(5):385-397. doi: 10.1038/s41577-024-01108-3. Epub 2024 Nov 19.
Fundamental discoveries in many aspects of mammalian physiology have been made using laboratory mice as research models. These studies have been facilitated by the genetic tractability and inbreeding of such mice, the large set of immunological reagents that are available, and the establishment of environmentally controlled, high-throughput facilities. Such facilities typically include barriers to keep the mouse colonies free of pathogens and the frequent re-derivation of the mice severely limits their commensal flora. Because humans have co-evolved with microorganisms and are exposed to a variety of pathogens, a growing community of researchers posits that preclinical disease research can be improved by studying mice in the context of the microbiota and pathogens that they would encounter in the natural world. Here, we provide a perspective of how these different approaches can be combined and integrated to improve existing mouse models to enhance our understanding of disease mechanisms and develop new therapies for humans. We also propose that the term 'mice with natural microbiota' is more appropriate for describing these models than existing terms such as 'dirty mice'.
在哺乳动物生理学的许多方面，利用实验室小鼠作为研究模型已取得了基础性发现。这些研究得益于此类小鼠的遗传易处理性和近亲繁殖、大量可用的免疫试剂以及环境可控的高通量设施的建立。此类设施通常设有屏障以保持小鼠群体无病原体，而小鼠的频繁重新培育严重限制了它们的共生菌群。由于人类与微生物共同进化并接触多种病原体，越来越多的研究人员认为，通过在小鼠遇到的微生物群和病原体的背景下研究小鼠，可以改进临床前疾病研究。在此，我们阐述了如何将这些不同方法结合与整合，以改进现有的小鼠模型，增进我们对疾病机制的理解，并为人类开发新疗法。我们还提议，“具有天然微生物群的小鼠”这一术语比诸如“脏小鼠”等现有术语更适合描述这些模型。
