Vertically Transmitted Fecal IgA Levels Determine Extra-Chromosomal Phenotypic Variation

Moon C, Baldridge MT, Wallace MA, Burnham CA, Virgin HW, Stappenbeck TS.

Nature. 2015 Feb 16. doi: 10.1038/nature14139. [Epub ahead of print]

Phenotypic variation between apparently genetically identical mice at different facilities/institutions has been a challenge facing investigators working in many different murine experimental systems. Differences in commensal microbiota between institutions is thought to be a potential culprit in this variation. It is known that the intestinal microbiota is inherited by the progeny from the mother in conventionally-raised mice. In this study, we showed that heritable, microbially-driven, dichotomous fecal IgA levels in wild-type mice within the same facility mimic the effects of chromosomal mutations. We observed in multiple facilities that vertically-transmissible bacteria in IgA-low mice dominantly lower fecal IgA levels in IgA-high mice after co-housing or fecal transplantation. In response to injury, IgA-low mice showed increased damage that was transferable by fecal transplantation and driven by fecal IgA differences. We found that bacteria from IgA-low mice degrade the secretory component of secretory IgA as well as IgA itself. These data indicated that phenotypic comparisons between mice must take into account the non-chromosomal hereditary variation between different breeders. We propose that fecal IgA levels can serve as one readily measurable marker of microbial variability between mice, and conclude that controlling for microbial variation between experimental mice byco-housing and/or fecal transplantation can enable the analysis of progeny from different dams within and between facilities or institutions. PubMed: 25686606