Laboratory mice born to wild mice have natural microbiota and model human immune responses
Laboratory mice born to wild mice have natural microbiota and model human immune responses
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DOI：
10.1126/science.aaw4361
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发表时间：
2019-08-02
期刊：
影响因子：
56.9
通讯作者：
Rehermann, Barbara
中科院分区：
文献类型：
--
作者：
Rosshart, Stephan P.;Herz, Jasmin;Rehermann, Barbara
实验室小鼠研究对于理解基本生物现象至关重要，但也有局限性。这包括由于微生物群不同而导致的结果冲突和有限的转化研究价值。为了解决这两个缺点，我们将C57BL/6胚胎移植到野生小鼠身上，创造了“野生小鼠”。这些小鼠在所有身体部位都具有天然的微生物群和病原体，并且具有C57BL/6小鼠的易处理遗传。野生动物的细菌微生物组、真菌组和病毒组影响多个器官的免疫景观。他们的肠道微生物群比实验室微生物群更有竞争力，并表现出对环境挑战的适应力。野生动物，但不是传统的实验室小鼠，在两项临床前研究中复制了人类的免疫反应。结合天然微生物群和病原体的模型可以提高生物医学研究的可重复性，增加从实验室到床边的安全性和免疫学研究的成功。
Laboratory mouse studies are paramount for understanding basic biological phenomena but also have limitations. These include conflicting results caused by divergent microbiota and limited translational research value. To address both shortcomings, we transferred C57BL/6 embryos into wild mice, creating "wildlings." These mice have a natural microbiota and pathogens at all body sites and the tractable genetics of C57BL/6 mice. The bacterial microbiome, mycobiome, and virome of wildlings affect the immune landscape of multiple organs. Their gut microbiota outcompete laboratory microbiota and demonstrate resilience to environmental challenges. Wildlings, but not conventional laboratory mice, phenocopied human immune responses in two preclinical studies. A combined natural microbiota- and pathogen-based model may enhance the reproducibility of biomedical studies and increase the bench-to-bedside safety and success of immunological studies.