Vertically transmitted faecal IgA levels determine extra-chromosomal phenotypic variation
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The proliferation of genetically modified mouse models has exposed phenotypic variation between investigators and institutions that has been challenging to control. In many cases, the microbiota is the presumed cause of the variation. Current solutions to account for phenotypic variability include littermate and maternal controls or defined microbial consortia in gnotobiotic mice. In conventionally raised mice, the microbiome is transmitted from the dam. Here we show that microbially driven dichotomous faecal immunoglobulin-A (IgA) levels in wild-type mice within the same facility mimic the effects of chromosomal mutations. We observe in multiple facilities that vertically transmissible bacteria in IgA-low mice dominantly lower faecal IgA levels in IgA-high mice after co-housing or faecal transplantation. In response to injury, IgA-low mice show increased damage that is transferable by faecal transplantation and driven by faecal IgA differences. We find that bacteria from IgA-low mice degrade the secretory component of secretory IgA as well as IgA itself. These data indicate that phenotypic comparisons between mice must take into account the non-chromosomal hereditary variation between different breeders. We propose faecal IgA as one marker of microbial variability and conclude that co-housing and/or faecal transplantation enables analysis of progeny from different dams.
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The intestinal microbiota can degrade IgA, which plays a key role in mucosal immunology, and mice with documented degradation of secretory IgA are more susceptible to chemically-induced colitis.
“It has been shown that the intestinal microbiota can degrade IgA, which plays a key role in mucosal immunology, and mice with documented degradation of secretory IgA are more susceptible to chemically-induced colitis.152”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [152]
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- Authors
- Moon, C., Baldridge, M. T., Wallace, M. A., Burnham, C.-A. D., Virgin, H. W., & Stappenbeck, T. S.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Virgin, Herbert W.
- Stappenbeck, Thaddeus S.
- ORCID
- Venue
- Nature
- Published
- 2015-02-16
- Volume
- 521
- Issue
- 7550
- Pages
- 90-93
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4425643
- OpenAlex
- W2086224292
- Cited by
- 268
- References
- 36
- Citations by year
- 2026: 9 · 2025: 15 · 2024: 24 · 2023: 22 · 2022: 18 · 2021: 37 · 2020: 29 · 2019: 27 · 2018: 24 · 2017: 21 · 2016: 28 · 2015: 13
- FWCI
- 12.44
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health (R01OD011170)
- National Cancer Institute (T32CA009547)
- National Institute of Allergy and Infectious Diseases (AI08488702, T32AI007163)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK7161907, R01DK071619, R01DK097079, R01DK101354, P30DK052574)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30AR048335)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Keywords
- vertical transmission, gut microbiota, phenotypic variability, wild-type mice, cohousing, secretory component, experimental replication, inter-laboratory variability, injury response
- MeSH terms
- Ampicillin, Anaerobiosis, Animals, Feces, Female, Immunoglobulin A, Immunoglobulin A, Secretory, Male, Mutation, Phenotype, Secretory Component, Reproducibility of Results, Biomarkers, Chromosomes, Mammalian, Mice, Microbiota
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