• KSBNS 2024


Original Article

Exp Neurobiol 2018; 27(2): 103-111

Published online April 30, 2018

© The Korean Society for Brain and Neural Sciences

Genetic Ablation of EWS RNA Binding Protein 1 (EWSR1) Leads to Neuroanatomical Changes and Motor Dysfunction in Mice

Yeojun Yoon1†, Hasang Park1†, Sangyeon Kim1†, Phuong T. Nguyen2†, Seung Jae Hyeon2†, Sooyoung Chung2, Hyeonjoo Im2, Junghee Lee3,4, Sean Bong Lee5* and Hoon Ryu2,3,4*

1Yonsei University College of Medicine, Seoul 03722, 2Center for Neuromedicine and Neuroscience, Brain Science Institute, Korea Institute of Science and Technology, Seoul 02792, Korea, 3VA Boston Healthcare System, Boston, MA 02130, 4Boston University Alzheimer’s Disease Center and Department of Neurology, Boston University School of Medicine, Boston, MA 02118, 5Department of Pathology & Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA

Correspondence to: *To whom correspondence should be addressed.
Sean Bong Lee, TEL: 1-504-988-1331, FAX: 1-504-988-7389
Hoon Ryu, TEL: 1-857-364-5910, FAX: 1-857-364-4540
These authors are contributed equally

Received: March 4, 2018; Revised: April 13, 2018; Accepted: April 13, 2018

A recent study reveals that missense mutations of EWSR1 are associated with neurodegenerative disorders such as amyotrophic lateral sclerosis, but the function of wild-type (WT) EWSR1 in the central nervous system (CNS) is not known yet. Herein, we investigated the neuroanatomical and motor function changes in Ewsr1 knock out (KO) mice. First, we quantified neuronal nucleus size in the motor cortex, dorsal striatum and hippocampus of three different groups: WT, heterozygous Ewsr1 KO (+/−), and homozygous Ewsr1 KO (−/−) mice. The neuronal nucleus size was significantly smaller in the motor cortex and striatum of homozygous Ewsr1 KO (−/−) mice than that of WT. In addition, in the hippocampus, the neuronal nucleus size was significantly smaller in both heterozygous Ewsr1 KO (+/−) and homozygous Ewsr1 KO (−/−) mice. We then assessed motor function of Ewsr1 KO (−/−) and WT mice by a tail suspension test. Both forelimb and hindlimb movements were significantly increased in Ewsr1 KO (−/−) mice. Lastly, we performed immunohistochemistry to examine the expression of TH, DARPP-32, and phosphorylated (p)-DARPP-32 (Thr75) in the striatum and substantia nigra, which are associated with dopaminergic signaling. The immunoreactivity of TH and DARPP-32 was decreased in Ewsr1 KO (−/−) mice. Together, our results suggest that EWSR1 plays a significant role in neuronal morphology, dopaminergic signaling pathways, and motor function in the CNS of mice.

Graphical Abstract

Keywords: EWSR1, central nervous system (CNS), neuron, dopamine, DARPP-32, motor function