Tumor multiplicity in the ApcMin (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-ApcMin) crossed with either C57BL/6J or C57BL/6N wild-type mice. We also used complex microbiota targeted rederivation to rederive B6NB6JMF1-ApcMin 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-ApcMin 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.

中文翻译：

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肠道菌群通过ApcMin小鼠的B6 / J和B6 / N遗传背景调节差异性腺瘤的抑制作用。

CRC的ApcMin（Min）小鼠模型中的肿瘤多样性是一种经典的定量特征，受复杂的遗传和环境因素影响，因此是研究疾病修饰因子的理想平台。虽然不同的近交遗传背景对肿瘤的多重性具有很好的修饰作用，但尚不清楚诸如C57BL / 6J和C57BL6 / N等更密切相关的背景是否差异修饰了表型。此外，尚不清楚复杂的肠道菌群（GM）是否会影响这些背景菌株的作用。我们评估了从威斯康星大学McArdle实验室的原始小菌落产生的F1小鼠中的肿瘤多样性（C57BL / 6JMlcr-ApcMin）与C57BL / 6J或C57BL / 6N野生型小鼠杂交。我们还使用了复杂的微生物群靶向再活化技术，使用具有来自两个不同来源的复杂GM的替代水坝来繁殖B6NB6JMF1-ApcMin胚胎，从而确定了复杂GM的作用。B6 / J和B6 / N背景均显着抑制了肿瘤的多重性。但是，B6 / N背景比B6 / J具有更强的显性抑制作用。此外，我们观察到，复杂的GM可能会调节B6 / N介导的腺瘤阻抑，使得两个不同的社区在同基因的B6NB6JMF1-ApcMin小鼠中赋予不同的肿瘤多样性。尽管我们不能排除胚胎移植可能对母体产生的影响，但我们证明B6 / J和B6 / N对Min具有修饰作用，并且这些作用会因复合基因GM进一步改变。最重要的是