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

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 biomedicalresearch can advance efficiently and with optimal translatability. To do so requires constant assessment offactors that can modulate model phenotypes and development of means to control and even exploit suchmodulating factors. In the past decade, there has been an explosion of research on the role of one suchfactor, the gut microbiota (GM), in modulating murine models of disease. We and others have shown thatmultiple factors can influence the composition of GM and more importantly, that changes in the GM can altermodel phenotypes. With this in mind, the MU MMRRC seeks to develop means to provide models on differingcomplex GM that have optimal translatability. To this end, we have created colonies of mice that harbordiffering stable and well-characterized complex GM that represent the spectrum of GM seen in contemporaryrodent colonies. However, additional research is necessary to refine complex GM-associated experimentaldesign strategies. Most notably, there is need to incorporate other components of the GM such as viralinfections so that the GM of our laboratory mice better replicate the human condition. In this proposal, we willapply this concept to refinement and optimization of a major model for the study of SARS-CoV-2 infection, theB6.Cg-Tg(K18-ACE2)2Prlmn/J mouse. We will assess how increasing antigen exposure of mice throughsupplementation of standardized complex GMs with selected viral and bacterial agents will modulate thephenotype of this model. Results generated will be invaluable and immediately applicable and to ongoingstudies of the devastating COVID-19 pandemic and mice developed will be immediately available to thebiomedical research community. Moreover, this strategy can be readily applied to any additional models forSARS-CoV-2 infection that arise in the near future.