Multi-modal comparative phenotyping of knock-in mouse models of frontotemporal dementia/amyotrophic lateral sclerosis

Boyanova, S, Banks, G ORCID: https://orcid.org/0000-0002-8647-667X, Lipina, TV, Bains, RS, Forrest, H, Stewart, M, Carcolé, M, Milioto, C, Isaacs, AM, Wells, SE and Wiseman, FK, 2025. Multi-modal comparative phenotyping of knock-in mouse models of frontotemporal dementia/amyotrophic lateral sclerosis. Disease Models and Mechanisms, 18 (8): dmm052324. ISSN 1754-8403

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Abstract

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are progressive adult-onset neurodegenerative diseases with overlapping pathological and genetic origins. They are caused by multiple underlying mechanisms leading to a common collection of clinical features that occur in a spectrum. Here, we report side-by-side longitudinal behavioural, cognitive and sensory phenotyping of two mouse models of ALS/FTD, to determine which aspects of the disease they recapitulate. We used knock-in models, in which the endogenous mouse orthologues of the C9orf72 and TARDBP (encoding TDP-43) genes have been altered to model specific molecular aspects of ALS/FTD. We found that the C9orf72GR400/+ model exhibits age-related deficit in short-term memory and that parental genotype affects exploration activity in offspring. In the TardbpQ331K/Q331K model, we found age-related changes in weight, fat mass, locomotion and marble burying. In both models, we found no evidence of deficits in vision or olfactory habituation-dishabituation. These data provide new insight into genotype-phenotype relationships in these ALS/FTD mice, which can be used to inform model choice and experimental design in future research studies.

Item Type:	Journal article
Publication Title:	Disease Models and Mechanisms
Creators:	Boyanova, S., Banks, G., Lipina, T.V., Bains, R.S., Forrest, H., Stewart, M., Carcolé, M., Milioto, C., Isaacs, A.M., Wells, S.E. and Wiseman, F.K.
Publisher:	The Company of Biologists
Date:	August 2025
Volume:	18
Number:	8
ISSN:	1754-8403
Identifiers:	Number Type 10.1242/dmm.052324 DOI 2492768 Other
Rights:	© 2025. Published by The Company of Biologists. 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.
Divisions:	Schools > School of Science and Technology
Record created by:	Jonathan Gallacher
Date Added:	03 Sep 2025 15:05
Last Modified:	03 Sep 2025 15:05
URI:	https://irep.ntu.ac.uk/id/eprint/54292

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