Watkins, J., Ghosh, A., Keerie, A.F.A. et al. (3 more authors) (2020) Female sex mitigates motor and behavioural phenotypes in TDP-43Q331K knock-in mice. Scientific Reports, 10 (1). 19220.
Abstract
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are overlapping neurodegenerative disorders. ALS is more commonly seen in men than women and the same may be the case for FTD. Preclinical models demonstrating sex-specific vulnerability may help to understand female resistance to ALS-FTD and thereby identify routes to therapy. We previously characterised a TDP-43Q331K knock-in mouse, which demonstrated behavioural phenotypes reminiscent of ALS-FTD in males. Here we present our behavioural observations of female TDP-43Q331K mutants. Female TDP-43Q331K knock-in mice displayed increased weight relative to wild-type and increased food intake at 20 months of age, much later than previously observed in male mutants. Spontaneous digging behaviour was initially normal and only declined in mutants in the second year of life. Gait analysis using Catwalk (https://www.noldus.com/catwalk-xt) found significant deficits in the second year of life, while nocturnal running behaviour was attenuated from ~ 250 days of life. These results indicate that while female TDP-43Q331K knock-in mice do display progressive behavioural phenotypes, these are less severe than we previously noted in male mutants. Further studies of male and female TDP-43Q331K knock-in mice may help to unravel the mechanisms underlying sex-specific vulnerability in ALS-FTD.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number MOTOR NEURONE DISEASE ASSOCIATION Mead/Jun16/900-790 Motor Neurone Disease Association MNDA-SITraN/Apr13/983-797 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 09 Nov 2020 10:30 |
Last Modified: | 03 Jun 2021 08:34 |
Status: | Published |
Publisher: | Springer Science and Business Media LLC |
Refereed: | Yes |
Identification Number: | 10.1038/s41598-020-76070-w |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:167751 |