近日，美国国立卫生研究院的Stephan P. Rosshart研究组合作揭示了由野生小鼠生的实验小鼠具有天然的微生物菌群，并能模拟人类的免疫反应。该研究于2019年8月2日发表于国际学术期刊《科学》上。
实验小鼠的研究对于理解基本的生物现象至关重要，但也有其局限性。这包括由于不同的微生物群与有限的转化研究价值所引起的相互矛盾的结果。为了解决这两个缺点，研究人员将C57BL/6胚胎移植到野生小鼠体内，创造了“野生鼠”。这些小鼠全身上下都具有天然的微生物菌群和病原体，并具有C57BL/6小鼠的可控遗传背景。野生鼠的细菌群、真菌群以及病毒群影响了多个器官的免疫状态。其肠道微生物组压制了实验微生物组，并显示出对环境挑战的适应力。野生鼠在两个临床前研究中模拟出人类的免疫响应，但传统实验小鼠却不行。因此，一个具有天然微生物组与病原体的模型可以增强生物医学研究的可重复性，并能够增加临床转化的安全性与免疫学研究的成功性。
附：英文原文
Title: Laboratory mice born to wild mice have natural microbiota and model human immune responses
Author: Stephan P. Rosshart, Jasmin Herz, Brian G. Vassallo, Ashli Hunter, Morgan K. Wall, Jonathan H. Badger, John A. McCulloch, Dimitrios G. Anastasakis, Aishe A. Sarshad, Irina Leonardi, Nicholas Collins, Joshua A. Blatter, Seong-Ji Han, Samira Tamoutounour, Svetlana Potapova, Mark B. Foster St. Claire, Wuxing Yuan, Shurjo K. Sen, Matthew S. Dreier, Benedikt Hild, Markus Hafner, David Wang, Iliyan D. Iliev, Yasmine Belkaid, Giorgio Trinchieri, Barbara Rehermann
Issue&Volume: Vol 365 Issue 6452
Abstract: 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.
DOI: 10.1126/science.aaw4361
Source: https://science.sciencemag.org/content/365/6452/eaaw4361