| First Author | Moskowitz JE | Year | 2019 |
| Journal | Mamm Genome | Volume | 30 |
| Issue | 9-10 | Pages | 237-244 |
| PubMed ID | 31549210 | Mgi Jnum | J:281657 |
| Mgi Id | MGI:6377331 | Doi | 10.1007/s00335-019-09814-3 |
| Citation | Moskowitz JE, et al. (2019) The gut microbiota modulates differential adenoma suppression by B6/J and B6/N genetic backgrounds in Apc(Min) mice. Mamm Genome 30(9-10):237-244 |
| abstractText | Tumor multiplicity in the Apc(Min) (Min) mouse model of CRC is a classic quantitative trait that is subject to complex genetic and environmental factors, and therefore serves as an ideal platform to study modifiers of disease. While disparate inbred genetic backgrounds have well-characterized modifying effects on tumor multiplicity, it is unclear whether more closely related backgrounds such as C57BL/6J and C57BL6/N differentially modify the phenotype. Furthermore, it is unknown whether the complex gut microbiota (GM) influences the effects of these background strains. We assessed tumor multiplicity in F1 mice generated from the original Min colony from the McArdle Laboratory at the University of Wisconsin (C57BL/6JMlcr-Apc(Min)) crossed with either C57BL/6J or C57BL/6N wild-type mice. We also used complex microbiota targeted rederivation to rederive B6NB6JMF1-Apc(Min) embryos using surrogate dams harboring complex GMs from two different sources to determine the effects of complex GM. Both B6/J and B6/N backgrounds significantly repressed tumor multiplicity. However, the B6/N background conferred a stronger dominant suppressive effect than B6/J. Moreover, we observed that complex GM likely modulated B6/N-mediated adenoma repression such that two distinct communities conferred differential tumor multiplicity in isogenic B6NB6JMF1-Apc(Min) mice. Although we cannot rule out possible maternal effects of embryo transfer, we show that B6/J and B6/N have modifier effects on Min, and these effects are further altered by the complex GM. Foremost, strict attention to genetic background and environmental variables influencing the GM is critical to enhance reproducibility in models of complex disease traits. |
