Brief Research Report ARTICLE
Lowering EphA4 does not ameliorate disease in a mouse model for severe spinal muscular atrophy
- 1VIB & KU Leuven Center for Brain & Disease Research, Belgium
- 2University Hospitals Leuven, Belgium
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: spinal muscular atrophy, SMA, EphA4, Neuromuscular Junction, sprouting
Received: 10 Sep 2019;
Accepted: 31 Oct 2019.
Copyright: © 2019 Poppe, Smolders, Rué, Timmers, Lenaerts, Storm, Schoonaert, de Boer, Van Damme, Van Den Bosch, Robberecht and Lemmens. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Mx. Lindsay Poppe, VIB & KU Leuven Center for Brain & Disease Research, Leuven, Belgium, email@example.com