Boyanova, Sevda;
Banks, Gareth;
Lipina, Tatiana V;
Bains, Rasneer Sonia;
Forrest, Hamish;
Stewart, Michelle;
Carcolé, Mireia;
... Wiseman, Frances K; + view all
(2025)
Multi-modal comparative phenotyping of knock-in mouse models of frontotemporal dementia/amyotrophic lateral sclerosis.
Disease Models & Mechanisms
, 18
(8)
, Article dmm052324. 10.1242/dmm.052324.
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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.
| Type: | Article |
|---|---|
| Title: | Multi-modal comparative phenotyping of knock-in mouse models of frontotemporal dementia/amyotrophic lateral sclerosis |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1242/dmm.052324 |
| Publisher version: | https://doi.org/10.1242/dmm.052324 |
| Language: | English |
| Additional information: | Copyright © 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. |
| Keywords: | Amyotrophic lateral sclerosis, Frontotemporal dementia, Mouse phenotyping |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > UK Dementia Research Institute |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10212943 |
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