Sleigh, J;
Tosolini, A;
Gordon, D;
Devoy, A;
Fratta, P;
Fisher, E;
Talbot, K;
(2020)
Mice carrying ALS mutant TDP-43, but not mutant FUS, display in vivo defects in axonal transport of signalling endosomes.
Cell Reports
, 30
(11)
pp. 3655-3662.
10.1016/j.celrep.2020.02.078.
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Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neurodegenerative disease resulting from a complex interplay between genetics and environment. Impairments in axonal transport have been identified in several ALS models, but in vivo evidence remains limited, thus their pathogenetic importance remains to be fully resolved. We therefore analyzed the in vivo dynamics of retrogradely transported, neurotrophin-containing signaling endosomes in nerve axons of two ALS mouse models with mutations in the RNA processing genes TARDBP and FUS. TDP-43M337V mice, which show neuromuscular pathology without motor neuron loss, display axonal transport perturbations manifesting between 1.5 and 3 months and preceding symptom onset. Contrastingly, despite 20% motor neuron loss, transport remained largely unaffected in FusΔ14/+ mice. Deficiencies in retrograde axonal transport of signaling endosomes are therefore not shared by all ALS-linked genes, indicating that there are mechanistic distinctions in the pathogenesis of ALS caused by mutations in different RNA processing genes.
| Type: | Article |
|---|---|
| Title: | Mice carrying ALS mutant TDP-43, but not mutant FUS, display in vivo defects in axonal transport of signalling endosomes |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.celrep.2020.02.078 |
| Publisher version: | https://doi.org/10.1016/j.celrep.2020.02.078 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | amyotrophic lateral sclerosis, ALS, intravital imaging, motor neuron disease, MNDRNA-binding protein, TARDBP |
| 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 > Department of Neuromuscular Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10092003 |
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