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

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.