Badger, S.E. orcid.org/0009-0009-3696-8578, Coldicott, I., Kyrgiou-Balli, E. et al. (7 more authors) (2025) A bacterial artificial chromosome mouse model of amyotrophic lateral sclerosis manifests ‘space cadet syndrome’ on two FVB backgrounds. Disease Models & Mechanisms, 18 (2). ISSN 1754-8403
Abstract
C9orf72-related amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD) has proven difficult to model in mice. Liu et al. (2016) reported a bacterial artificial chromosome (BAC) transgenic mouse displaying behavioural, motor and pathological abnormalities. This was followed by multiple laboratories independently refuting and confirming phenotypes. A proposed explanation centred on the use of different FVB background lines (from The Jackson Laboratory and Janvier Labs). 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 indicate that the differences previously reported are not due to C9orf72 status and highlight the importance of using genetic backgrounds that do not confound interpretation of neurodegenerative phenotypes.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2025. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
Keywords: | Amyotrophic lateral sclerosis; Frontotemporal dementia; Bacterial artificial chromosome; Mouse model; FVB/N; Space cadet syndrome |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine and Population Health |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 19 Feb 2025 15:14 |
Last Modified: | 19 Feb 2025 15:14 |
Status: | Published |
Publisher: | The Company of Biologists |
Refereed: | Yes |
Identification Number: | 10.1242/dmm.052221 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:223441 |