Frontiers in Neuroscience (Nov 2019)
Lowering EphA4 Does Not Ameliorate Disease in a Mouse Model for Severe Spinal Muscular Atrophy
- Lindsay Poppe,
- Lindsay Poppe,
- Silke Smolders,
- Silke Smolders,
- Laura Rué,
- Laura Rué,
- Mieke Timmers,
- Mieke Timmers,
- Annette Lenaerts,
- Annette Lenaerts,
- Annet Storm,
- Annet Storm,
- Lies Schoonaert,
- Lies Schoonaert,
- Antina de Boer,
- Antina de Boer,
- Philip Van Damme,
- Philip Van Damme,
- Philip Van Damme,
- Ludo Van Den Bosch,
- Ludo Van Den Bosch,
- Wim Robberecht,
- Wim Robberecht,
- Robin Lemmens,
- Robin Lemmens,
- Robin Lemmens
Affiliations
- Lindsay Poppe
- Department of Neurosciences, Experimental Neurology and Leuven Brain Institute (LBI), KU Leuven – University of Leuven, Leuven, Belgium
- Lindsay Poppe
- Laboratory of Neurobiology, VIB – KU Leuven Center for Brain & Disease Research, Leuven, Belgium
- Silke Smolders
- Department of Neurosciences, Experimental Neurology and Leuven Brain Institute (LBI), KU Leuven – University of Leuven, Leuven, Belgium
- Silke Smolders
- Laboratory of Neurobiology, VIB – KU Leuven Center for Brain & Disease Research, Leuven, Belgium
- Laura Rué
- Department of Neurosciences, Experimental Neurology and Leuven Brain Institute (LBI), KU Leuven – University of Leuven, Leuven, Belgium
- Laura Rué
- Laboratory of Neurobiology, VIB – KU Leuven Center for Brain & Disease Research, Leuven, Belgium
- Mieke Timmers
- Department of Neurosciences, Experimental Neurology and Leuven Brain Institute (LBI), KU Leuven – University of Leuven, Leuven, Belgium
- Mieke Timmers
- Laboratory of Neurobiology, VIB – KU Leuven Center for Brain & Disease Research, Leuven, Belgium
- Annette Lenaerts
- Department of Neurosciences, Experimental Neurology and Leuven Brain Institute (LBI), KU Leuven – University of Leuven, Leuven, Belgium
- Annette Lenaerts
- Laboratory of Neurobiology, VIB – KU Leuven Center for Brain & Disease Research, Leuven, Belgium
- Annet Storm
- Department of Neurosciences, Experimental Neurology and Leuven Brain Institute (LBI), KU Leuven – University of Leuven, Leuven, Belgium
- Annet Storm
- Laboratory of Neurobiology, VIB – KU Leuven Center for Brain & Disease Research, Leuven, Belgium
- Lies Schoonaert
- Department of Neurosciences, Experimental Neurology and Leuven Brain Institute (LBI), KU Leuven – University of Leuven, Leuven, Belgium
- Lies Schoonaert
- Laboratory of Neurobiology, VIB – KU Leuven Center for Brain & Disease Research, Leuven, Belgium
- Antina de Boer
- Department of Neurosciences, Experimental Neurology and Leuven Brain Institute (LBI), KU Leuven – University of Leuven, Leuven, Belgium
- Antina de Boer
- Laboratory of Neurobiology, VIB – KU Leuven Center for Brain & Disease Research, Leuven, Belgium
- Philip Van Damme
- Department of Neurosciences, Experimental Neurology and Leuven Brain Institute (LBI), KU Leuven – University of Leuven, Leuven, Belgium
- Philip Van Damme
- Laboratory of Neurobiology, VIB – KU Leuven Center for Brain & Disease Research, Leuven, Belgium
- Philip Van Damme
- Department of Neurology, University Hospitals Leuven, Leuven, Belgium
- Ludo Van Den Bosch
- Department of Neurosciences, Experimental Neurology and Leuven Brain Institute (LBI), KU Leuven – University of Leuven, Leuven, Belgium
- Ludo Van Den Bosch
- Laboratory of Neurobiology, VIB – KU Leuven Center for Brain & Disease Research, Leuven, Belgium
- Wim Robberecht
- Department of Neurosciences, Experimental Neurology and Leuven Brain Institute (LBI), KU Leuven – University of Leuven, Leuven, Belgium
- Wim Robberecht
- Department of Neurology, University Hospitals Leuven, Leuven, Belgium
- Robin Lemmens
- Department of Neurosciences, Experimental Neurology and Leuven Brain Institute (LBI), KU Leuven – University of Leuven, Leuven, Belgium
- Robin Lemmens
- Laboratory of Neurobiology, VIB – KU Leuven Center for Brain & Disease Research, Leuven, Belgium
- Robin Lemmens
- Department of Neurology, University Hospitals Leuven, Leuven, Belgium
- DOI
- https://doi.org/10.3389/fnins.2019.01233
- Journal volume & issue
-
Vol. 13
Abstract
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.
Keywords
