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Chronic Salmonella Infection Induced Intestinal Fibrosis

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Vertically transmitted faecal IgA levels determine extra-chromosomal phenotypic variation.

Clara Moon¹, Megan T Baldridge¹, Meghan A Wallace¹

¹Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.

|February 18, 2015

Summary

Microbial differences in mice cause significant phenotypic variation, mimicking genetic mutations. Faecal immunoglobulin-A (IgA) levels can indicate this variability, suggesting co-housing or transplantation for consistent research.

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Area of Science:

Immunology
Microbiology
Genetics

Background:

Genetically modified mouse models exhibit phenotypic variation, often attributed to microbiota differences.
Existing methods to control variability include littermate controls or gnotobiotic models with defined microbial consortia.

Purpose of the Study:

To investigate the role of microbial factors, specifically fecal immunoglobulin-A (IgA) levels, in causing phenotypic variation in conventionally raised mice.
To identify a marker for microbial variability and propose methods to mitigate its effects on experimental outcomes.

Main Methods:

Comparison of fecal IgA levels in wild-type mice across different facilities.
Co-housing and fecal microbiota transplantation experiments between mice with high and low IgA levels.
Analysis of bacterial degradation of IgA and its secretory component.

Main Results:

Dichotomous fecal IgA levels were observed within the same facility, mimicking chromosomal mutation effects.
Bacteria from IgA-low mice reduced IgA levels in IgA-high mice via co-housing or transplantation.
IgA-low mice exhibited increased, transferable damage in response to injury, linked to IgA differences.
Bacteria from IgA-low mice were found to degrade secretory IgA and IgA itself.

Conclusions:

Non-chromosomal hereditary variation due to microbial factors must be considered in mouse studies.
Fecal IgA serves as a marker for microbial variability.
Co-housing and fecal transplantation can help standardize experiments using mice from different dams.