Lowering EphA4 Does Not Ameliorate Disease in a Mouse Model for Severe Spinal Muscular Atrophy.
EphA4
motor neuron
neuromuscular junction
spinal muscular atrophy
sprouting
Journal
Frontiers in neuroscience
ISSN: 1662-4548
Titre abrégé: Front Neurosci
Pays: Switzerland
ID NLM: 101478481
Informations de publication
Date de publication:
2019
2019
Historique:
received:
10
09
2019
accepted:
31
10
2019
entrez:
6
12
2019
pubmed:
6
12
2019
medline:
6
12
2019
Statut:
epublish
Résumé
EphA4 is a receptor of the Eph-ephrin system, which plays an important role in axon guidance during development. Previously, we identified EphA4 as a genetic modifier of amyotrophic lateral sclerosis (ALS) in both zebrafish and rodent models, via modulation of the intrinsic vulnerability, and re-sprouting capacity of motor neurons. Moreover, loss of EphA4 rescued the motor axon phenotype in a zebrafish model of spinal muscular atrophy (SMA). Similar to ALS, SMA is a neurodegenerative disorder affecting spinal motor neurons resulting in neuromuscular junction (NMJ) denervation, muscle atrophy and paralysis. In this study, we investigated the disease modifying potential of reduced EphA4 protein levels in the SMNΔ7 mouse model for severe SMA. Reduction of EphA4 did not improve motor function, survival, motor neuron survival or NMJ innervation. Our data suggest that either lowering EphA4 has limited therapeutic potential in SMA or that the clinical severity hampers the potential beneficial role of EphA4 reduction in this mouse model for SMA.
Identifiants
pubmed: 31803009
doi: 10.3389/fnins.2019.01233
pmc: PMC6877733
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1233Informations de copyright
Copyright © 2019 Poppe, Smolders, Rué, Timmers, Lenaerts, Storm, Schoonaert, de Boer, Van Damme, Van Den Bosch, Robberecht and Lemmens.
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