Translational Rodent Models for Research on Parasitic Protozoa-A Review of Confounders and Possibilities.
Translational Rodent Models for Research on Parasitic Protozoa-A Review of Confounders and Possibilities.
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DOI：
10.3389/fcimb.2017.00238
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发表时间：
2017
影响因子：
5.7
通讯作者：
Seeber F
中科院分区：
文献类型：
--
作者：
Ehret T;Torelli F;Klotz C;Pedersen AB;Seeber F
啮齿动物，特别是小家鼠，作为生物医学研究中人类疾病的模型，具有悠久而宝贵的历史，尽管它们的转化价值在许多情况下受到挑战。我们提供了一些例子，其中啮齿动物已次优的模型，人类生物学和讨论的混杂因素，影响实验，并可能解释一些误导性的结果。啮齿类动物感染原生动物寄生虫也不例外，需要密切考虑模型的选择。我们专注于近交，远交和野生动物之间的显着差异，以及微生物等因素的重要性，这些因素作为感染实验中的关键变量而受到关注。通常，为了方便选择小鼠或大鼠模型，例如，这取决于机构中的可用性，而不是对他们是否提供了给定问题的答案进行公正的评价。除了对翻译成功或失败的一般性讨论外，我们还提供了一些例子，其中在选定的实验室啮齿动物中感染单细胞寄生虫得到了矛盾或误导性的结果，并在可能的情况下讨论了原因。我们提出了新兴的替代传统的啮齿动物模型，如人源化小鼠和类器官原代细胞培养。所谓的重组近交系，如协作杂交收集也是某些挑战的潜在解决方案。此外，我们强调使用野生啮齿动物的某些免疫学，生态学和/或行为问题的优势。实验挑战（例如，物种特异性试剂的可获得性）也进行了讨论。我们的目的是促进传统和新的翻译啮齿动物模型的研究，可以补充现有的小鼠和大鼠模型的寄生原虫的关键判断。
Rodents, in particular Mus musculus, have a long and invaluable history as models for human diseases in biomedical research, although their translational value has been challenged in a number of cases. We provide some examples in which rodents have been suboptimal as models for human biology and discuss confounders which influence experiments and may explain some of the misleading results. Infections of rodents with protozoan parasites are no exception in requiring close consideration upon model choice. We focus on the significant differences between inbred, outbred and wild animals, and the importance of factors such as microbiota, which are gaining attention as crucial variables in infection experiments. Frequently, mouse or rat models are chosen for convenience, e.g., availability in the institution rather than on an unbiased evaluation of whether they provide the answer to a given question. Apart from a general discussion on translational success or failure, we provide examples where infections with single-celled parasites in a chosen lab rodent gave contradictory or misleading results, and when possible discuss the reason for this. We present emerging alternatives to traditional rodent models, such as humanized mice and organoid primary cell cultures. So-called recombinant inbred strains such as the Collaborative Cross collection are also a potential solution for certain challenges. In addition, we emphasize the advantages of using wild rodents for certain immunological, ecological, and/or behavioral questions. The experimental challenges (e.g., availability of species-specific reagents) that come with the use of such non-model systems are also discussed. Our intention is to foster critical judgment of both traditional and newly available translational rodent models for research on parasitic protozoa that can complement the existing mouse and rat models.