实验室老鼠是人体免疫系统的差模型

StephenW

Lab Mice Are Poor Models of the Human Immune System

But housing ultraclean lab rodents with “dirty” mice from pet stores could help

    By Esther Landhuis on July 1, 2016


Credit: Thomas Fuchs

Scientists usually order laboratory mice online, but immunologist David Masopust went to more trouble. While doing research years ago at Emory University, he drove to a barn several hours away to trap the rodents himself. He suspected that commercially provided lab mice were missing some key immune cells because they had inexperienced immune systems—a result of being raised in extremely hygienic facilities. Masopust, now a professor at the University of Minnesota, went on to formally test his suspicion over the course of a decade and has found that it was correct: lab mice used by the scientific community and pharmaceutical world to test drugs and vaccines for human diseases are in some ways poor models of the human adult immune system.

As published this spring in the journal Nature, Masopust and his colleagues discovered that mice raised in germ-free facilities had immune systems that looked more like those of human babies than adults, as judged by the types of immune cells present and the genes that were active in those cells. For example, memory CD8+ T cells that serve as first responders to infection were virtually undetectable in adult lab mice but clearly present in barn mice and mice from pet stores. “We've ‘known’ this, but it's good to finally see it proven,” says Purvesh Khatri, a computational systems immunologist at Stanford University who was not involved in the study.

What is more, when the researchers housed “clean” lab mice with “dirty” pet store mice (which carried germs), about a fifth of the lab mice died of infections within a few months. The mice that survived, however, developed more robust immune repertoires, and the gene activity of their immune cells shifted to resemble those of adult humans. In follow-up experiments, those mice fought off bacterial infections just as well as mice vaccinated against the pathogens.

These results suggest that having lab mice share space with animals from the wild or from pet stores could give researchers a more realistic view of disease progression and treatment responses in human adults. Additionally, by showing that lab mice fail to model key immune features, the study could partially explain why therapeutics tested in animals often fail in human trials. “Variables that matter in the real world aren't present in controlled experiments,” Khatri explains.

This article was originally published with the title "Lab Mice Are Too Clean"

StephenW

实验室老鼠是人体免疫系统的模型差

但是，从宠物商店“脏”老鼠住房超净实验室老鼠可以帮助

    以斯帖Landhuis酒店于2016年7月1日


信用：托马斯·福克斯

科学家们通常在网上订购实验室老鼠，但免疫大卫马索普斯特去了更多的麻烦。虽然做研究年前在埃默里大学，他开车到谷仓里几个小时的路程捕获鼠类自己。他怀疑商家提供的服务实验鼠不翼而飞一些关键免疫细胞，因为他们有经验的免疫系统 - 一个在极其卫生设施被上升的结果。马索普斯特，现在在明尼苏达大学教授，后来上了十多年的历程正式测试他的怀疑和发现，这是正确的：科学界和医药界使用的实验室老鼠来测试人类疾病的药物和疫苗在某些方面的人类成人的免疫系统的差的模型。

由于今年春天发表在自然杂志，马索普斯特和他的同事发现，在无菌设施提出了小鼠看起来更象那些人类婴儿比成人的免疫系统，通过类型目前的免疫细胞和人的基因来判断活跃​​在这些细胞。例如，作为第一反应感染记忆CD8 + T细胞在成年实验鼠几乎检测不到，但显然存在于从宠物商店谷仓小鼠和小鼠。 “我们已经'知'，但它的好，终于看到它证明，”Purvesh卡特里，斯坦福大学的计算系统免疫谁没有参与这项研究说。

更重要的是，当研究人员安置与“脏”宠物店小鼠（其中进行细菌）“干净”的实验鼠，实验室老鼠的五分之一去世几个月内感染。存活，但是，开发了更有力的免疫全集的小鼠，和它们的免疫细胞的基因活性转移到类似那些成年人的。在后续实验中，那些老鼠击退细菌感染一样好接种病原体小鼠。

这些结果表明，具有从野生或从宠物商店动物实验室小鼠所占空间可以给研究者在人类成人疾病进展和治疗反应更现实的图。此外，通过展示实验室小鼠不能关键免疫功能模式，研究可以部分解释为什么在动物身上进行测试疗法往往在人体试验失败。 “在现实世界中重要的变量是不存在的对照实验中，”卡特里说。

这篇文章最初是标题发表了“实验室老鼠是太干净”