The Mutant Mouse Resource and Research Center at the University of Missouri

点击翻译按钮获取中文摘要

An overarching goal of the Mutant Mouse Resource and Research Center at the University of Missouri (MUMMRRC) is to provide refined mouse models to its users so that the broad range of disciplines in biomedical research can advance efficiently and with optimal translatability. To do so requires constant assessment of factors that can modulate model phenotypes and development of means to control and even exploit such modulating factors. In the past decade, there has been an explosion of research on the role of one such factor, the gut microbiota (GM), in modulating murine models of disease. We and others have shown that multiple factors can influence the composition of GM and more importantly, that changes in the GM can alter model phenotypes. With this in mind, the MU MMRRC seeks to develop means to provide models on differing complex GM that have optimal translatability. To this end, we have created colonies of mice that harbor differing stable and well-characterized complex GM that represent the spectrum of GM seen in contemporary rodent colonies. However, additional research is necessary to refine complex GM-associated experimental design strategies. Most notably, there is need to incorporate other components of the GM such as viral infections so that the GM of our laboratory mice better replicate the human condition. In this proposal, we will apply this concept to refinement and optimization of a major model for the study of SARS-CoV-2 infection, the B6.Cg-Tg(K18-ACE2)2Prlmn/J mouse. We will assess how increasing antigen exposure of mice through supplementation of standardized complex GMs with selected viral and bacterial agents will modulate the phenotype of this model. Results generated will be invaluable and immediately applicable and to ongoing studies of the devastating COVID-19 pandemic and mice developed will be immediately available to the biomedical research community. Moreover, this strategy can be readily applied to any additional models for SARS-CoV-2 infection that arise in the near future.