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培育具有不同标准化肠道微生物群特征的近交系 CD1 鼠群,用于复杂的靶向微生物群研究。

Development of outbred CD1 mouse colonies with distinct standardized gut microbiota profiles for use in complex microbiota targeted studies.

机构信息

Comparative Medicine Program, University of Missouri, Columbia, Missouri, United States of America.

University of Missouri Metagenomics Center, University of Missouri, Columbia, Missouri, United States of America.

出版信息

Sci Rep. 2018 Jul 4;8(1):10107. doi: 10.1038/s41598-018-28448-0.

DOI:10.1038/s41598-018-28448-0
PMID:29973630
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6031694/
Abstract

Studies indicate that the gut microbiota (GM) can significantly influence both local and systemic host physiologic processes. With rising concern for optimization of experimental reproducibility and translatability, it is essential to consider the GM in study design. However, GM profiles can vary between rodent producers making consistency between models challenging. To circumvent this, we developed outbred CD1 mouse colonies with stable, complex GM profiles that can be used as donors for a variety of GM transfer techniques including rederivation, co-housing, cross-foster, and fecal microbiota transfer (FMT). CD1 embryos were surgically transferred into CD1 or C57BL/6 surrogate dams that varied by GM composition and complexity to establish four separate mouse colonies harboring GM profiles representative of contemporary mouse producers. Using targeted 16S rRNA amplicon sequencing, subsequent female offspring were found to have similar GM profiles to surrogate dams. Furthermore, breeding colonies of CD1 mice with distinct GM profiles were maintained for nine generations, demonstrating GM stability within these colonies. To confirm GM stability, we shipped cohorts of these four colonies to collaborating institutions and found no significant variation in GM composition. These mice are an invaluable experimental resource that can be used to investigate GM effects on mouse model phenotype.

摘要

研究表明,肠道微生物群(GM)可以显著影响宿主的局部和全身生理过程。随着人们越来越关注优化实验的可重复性和可转化性,在研究设计中考虑 GM 是至关重要的。然而,由于不同的啮齿动物生产商之间 GM 谱存在差异,使得模型之间的一致性变得具有挑战性。为了解决这个问题,我们开发了具有稳定、复杂 GM 谱的远交 CD1 鼠群,可作为各种 GM 转移技术的供体,包括再衍生、共饲养、交叉寄养和粪便微生物群转移(FMT)。将 CD1 胚胎通过手术转移到 GM 组成和复杂程度不同的 CD1 或 C57BL/6 代孕母鼠体内,建立了四个具有代表当代鼠生产商 GM 谱的独立鼠群。使用靶向 16S rRNA 扩增子测序,发现随后的雌性后代具有与代孕母鼠相似的 GM 谱。此外,具有不同 GM 谱的 CD1 小鼠繁殖群维持了九代,表明这些群体内 GM 稳定。为了确认 GM 的稳定性,我们将这四个群体的一批小鼠运往合作机构,发现 GM 组成没有明显变化。这些小鼠是一种非常有价值的实验资源,可以用来研究 GM 对小鼠模型表型的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b16/6031694/3d5d2be51a02/41598_2018_28448_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b16/6031694/6cb04d81648d/41598_2018_28448_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b16/6031694/8a8435bb60ad/41598_2018_28448_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b16/6031694/f2af97d319c0/41598_2018_28448_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b16/6031694/d2a39d12717a/41598_2018_28448_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b16/6031694/7dbffda80a81/41598_2018_28448_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b16/6031694/3d5d2be51a02/41598_2018_28448_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b16/6031694/6cb04d81648d/41598_2018_28448_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b16/6031694/8a8435bb60ad/41598_2018_28448_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b16/6031694/f2af97d319c0/41598_2018_28448_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b16/6031694/d2a39d12717a/41598_2018_28448_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b16/6031694/7dbffda80a81/41598_2018_28448_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b16/6031694/3d5d2be51a02/41598_2018_28448_Fig6_HTML.jpg

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