Generating Mice with Diverse Microbial Experience

Abstract

Laboratory strains of mice are typically housed in specific pathogen-free facilities to minimize exposure to microbes. This method encourages uniformity in responses to experimentally induced parameters and reduces loss of animals, allowing for the survival and study of immunodeficient mice. However, the restrictions also limit physiologic relevance to humans, who are exposed to numerous microbes from birth. Recent evidence from several groups has demonstrated that exposure of laboratory mice to commensal and pathogenic microbes normally found in wild or pet store mice can dramatically impact the cellular makeup and function of the immune system. This article outlines procedures for exposing laboratory strains of mice to the diverse array of microbes typically found in pet store mice. Suggested methods for characterization of the immune system following this exposure are also described. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Cohousing laboratory strains of mice with pet store mice Support Protocol: Antibody staining of circulating immune cells and analysis by flow cytometry Basic Protocol 2: Exposure of laboratory strains of mice to fomite bedding.

Keywords: T cells; microbial diversity; microbiome; mouse model; serology.

Figure 1.. Flow cytometry gating strategy for assessing immune cells after cohousing.

Blood was collected from either (A) a female C57BL6 SPF mouse or (B) a female C57BL6 mouse cohoused for 30 days with a pet store mouse. Blood was processed and stained with fluorescent antibodies as described in Support Protocol 1. Frequencies listed represent percentages of the parent population. Populations in red identify the largest consistently altered populations between SPF and cohoused mice. These and other expected differences in the frequency of antibody stained cells are listed in Table 2.