Exp Neurobiol.
2018 Apr;27(2):103-111. 10.5607/en.2018.27.2.103.
Genetic Ablation of EWS RNA Binding Protein 1 (EWSR1) Leads to Neuroanatomical Changes and Motor Dysfunction in Mice
- Affiliations
-
- 1Yonsei University College of Medicine, Seoul 03722, Korea.
- 2Center for Neuromedicine and Neuroscience, Brain Science Institute, Korea Institute of Science and Technology, Seoul 02792, Korea. hoonryu@bu.edu
- 3VA Boston Healthcare System, Boston, MA 02130, USA.
- 4Boston University Alzheimer's Disease Center and Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA.
- 5Department of Pathology & Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA. slee30@tulane.edu
- KMID: 2410471
- DOI: http://doi.org/10.5607/en.2018.27.2.103
Abstract
- 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.
Keyword
- Full Text Links
-
- Actions
-
Cited
- CITED
-
- Close
- Share
-
- Similar articles
-
- Recent Advances in the Molecular Mechanisms and Therapeutic Strategies Targeting EWS/ETS in Ewing Sarcoma Family of Tumors
- A Case of Primary Cutaneous Extraskeletal Ewing Sarcoma on the Abdomen
- RNA Binding Protein as an Emerging Therapeutic Target for Cancer Prevention and Treatment
- RNA Regulation in Neurologic Disease and Cancer
- Induction of Apoptosis of Cancer Cells by Inhibition of Bcl-2 Expression
