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.