# The Mutant Mouse Resource and Research Center at the University of Missouri - Applied Research Section 1

> **NIH NIH U42** · UNIVERSITY OF MISSOURI-COLUMBIA · 2022 · $85,117

## Abstract

Applied Research section 1 – Project Summary
After decades of efforts to rid laboratory mice of pathogens and other subclinical microbes capable of
confounding research, there is an emerging realization that mice completely devoid of any and all viral,
bacterial, protozoal, and fungal pathogens including even the most questionable opportunists, are essentially
antigen-naïve and as such, may not serve as appropriate or ideal models of human disease. Several studies
have demonstrated that pet store and wild mice are qualitatively different from standard laboratory mice in
terms of circulating memory T cell and immunoglobulin profiles. This antigen-experienced immunophenotype
is consistently associated with a protective effect in models of infectious disease, intestinal inflammation, and
tumorigenesis, and this immunophenotype can be transferred experimental via the gut microbiota (GM). In the
interests of biosecurity, worker safety, and reproducible data however, it would be ideal if the antigen-
experienced immunophenotype could be induced in laboratory mice via experimental inoculation with the
appropriate microbes. Thus, the long-term objectives of this Applied Research section are to investigate and
develop methods of reproducibly inducing an antigen-experienced immunophenotype in laboratory mice which
confers a protective effect in disease models previously shown to be sensitive to these factors. The Specific
Aims are to 1) test the ability of two candidate bacterial ‘provocateurs’ of host immune responses, alongside a
viral control and in the context of two distinct GM communities, to induce the differentiation of effector memory
T cells and immunoglobulin production, and 2) to evaluate the susceptibility of mice in these experimental
antigen exposure groups to disease susceptibility using two commonly used mouse models of disease known
to differ in severity depending on the degree of previous host antigen exposure. Specifically, the microbial
agents to be evaluated include Helicobacter hepaticus, segmented filamentous bacteria (Candidatus
Savagella), and Murine Hepatitis Virus (MHV), and the models to be tested include Non-obese Diabetic (NOD)
mice and DSS-induced colitis. If traditional laboratory mice used in translational biomedical research are
universally more susceptible in disease models as suggested by recent studies, it essentially distorts our ability
to identify mechanisms and therapies of disease, wasting time and resources on ‘false positives’ that do not
translate to humans, and missing opportunities on ‘false negatives’ that show exaggerated toxicities that might
not be present in antigen-experienced individuals. The development and refinement of methods such as those
proposed in this Applied Research section will revolutionize biomedical research and increase efficiencies in
the development of therapeutics and discovery of mechanisms. Moreover, generation and provision of mice
with an antigen-experienced immunophenotype will ...

## Key facts

- **NIH application ID:** 10360485
- **Project number:** 5U42OD010918-23
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** Aaron Ericsson
- **Activity code:** U42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $85,117
- **Award type:** 5
- **Project period:** 2000-05-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10360485

## Citation

> US National Institutes of Health, RePORTER application 10360485, The Mutant Mouse Resource and Research Center at the University of Missouri - Applied Research Section 1 (5U42OD010918-23). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10360485. Licensed CC0.

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