Mordes et al. (2020) did not detect the survival or motor phenotypes in C9orf72 BAC transgenic mice originally described by Liu et al. (2016). We discuss methodological differences between the Mordes and Liu studies, several additional studies in which survival and motor phenotypes were found, and possible environmental and genetic effects. First, Nguyen et al. (2020) showed robust ALS/FTD phenotypes in C9-BAC versus non-transgenic (NT) mice and that α-GA₁ treatment improved survival, behavior, and neurodegeneration. The groups of Gelbard and Saxena also show decreased survival of C9-BAC versus NT mice and neuropathological and behavioral deficits similar to those shown by Liu et al. (2016). Although FVB/N mice can have seizures, increases in seizure severity and death of C9 and NT animals, which may mask C9 disease phenotypes, have been observed in recent C9-500 FVB/NJ-bred cohorts. In summary, we provide an update on phenotypes seen in FVB C9-BAC mice and additional details to successfully use this model. This Matters Arising Response paper addresses the Mordes et al. (2020) Matters Arising paper, published concurrently in Neuron.

莫德斯等人。(2020) 没有检测到Liu 等人最初描述的C9orf72 BAC 转基因小鼠的存活或运动表型。(2016)。我们讨论了 Mordes 和 Liu 研究之间的方法学差异、其他几项发现生存和运动表型的研究，以及可能的环境和遗传影响。首先，Nguyen 等人。(2020) 在 C9-BAC 与非转基因 (NT) 小鼠中显示出稳健的 ALS/FTD 表型，并且 α-GA ₁治疗改善了生存、行为和神经变性。Gelbard 和 Saxena 组还显示 C9-BAC 与 NT 小鼠相比存活率降低，以及与 Liu 等人所显示的相似的神经病理学和行为缺陷。(2016)。尽管 FVB/N 小鼠可能有癫痫发作，但在最近的 C9-500 FVB/NJ 饲养队列中观察到 C9 和 NT 动物癫痫发作严重程度和死亡的增加，这可能掩盖了 C9 疾病表型。总之，我们提供了在 FVB C9-BAC 小鼠中看到的表型的更新以及成功使用该模型的其他详细信息。这篇“出现问题的回应”论文针对 Mordes 等人。(2020) Matters Arising 论文，同时发表在Neuron 上。