Data for Detailed characterisation and comparison of the C9orf72 BAC mouse model of ALS/FTD on two FVB/N lines

The repository contains data for the paper titled Detailed characterisation and comparison of the C9orf72 BAC mouse model of ALS/FTD on two FVB/N lines.C9orf72-related amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD) has proven difficult to model in mice. Liu et al (2016, Neuron) reported a bacterial artificial chromosome (BAC) transgenic mouse manifesting behavioural, motor and pathological abnormalities. This was followed by multiple laboratories independently refuting (Mordes et al 2020, Neuron) and confirming (Nguyen et al 2020, Neuron) phenotypes. A proposed explanation centred on use of different FVB background lines (Jackson and Janvier laboratories). We studied C9orf72 BAC mice on both backgrounds and found significantly elevated levels of dipeptide repeat proteins, but no evidence of a transgene-associated phenotype. We observed seizures and a gradual decline in functional performance in transgenic and non-transgenic mice, irrespective of genetic background. The phenotype was in keeping with the so-called ‘space cadet syndrome’. Our findings confirm that the differences previously reported are not due to C9orf72 status and highlight the importance of using genetic backgrounds which do not confound interpretation of neurodegenerative phenotypes.

本存储库包含了题为《C9orf72 BAC小鼠模型在ALS/FTD中的详细表征和比较》的论文数据，涉及两种FVB/N品系。C9orf72相关肌萎缩侧索硬化症（ALS）/额颞叶痴呆（FTD）在老鼠模型中的模拟一直颇具挑战。Liu等人（2016年，《神经元》）报道了一种细菌人工染色体（BAC）转基因小鼠，该小鼠表现出行为、运动和病理学异常。随后，多个实验室独立地驳斥（Mordes等人2020年，《神经元》）并证实（Nguyen等人2020年，《神经元》）了表型。一种假设的解释集中在使用不同的FVB背景品系（Jackson和Janvier实验室）。我们研究了两种背景下的C9orf72 BAC小鼠，并发现双肽重复蛋白水平显著升高，但未发现与转基因相关的表型。我们在转基因和非转基因小鼠中观察到癫痫发作和功能表现的逐渐下降，无论遗传背景如何。该表型与所谓的‘太空兵综合征’相吻合。我们的研究证实，之前报道的差异并非由于C9orf72状态，并强调了使用不影响神经退行性表型解释的遗传背景的重要性。