A recent study reveals that missense mutations of 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 knock out (KO) mice. First, we quantified neuronal nucleus size in the motor cortex, dorsal striatum and hippocampus of three different groups: WT, heterozygous KO (+/-), and homozygous KO (-/-) mice. The neuronal nucleus size was significantly smaller in the motor cortex and striatum of homozygous KO (-/-) mice than that of WT. In addition, in the hippocampus, the neuronal nucleus size was significantly smaller in both heterozygous KO (+/-) and homozygous KO (-/-) mice. We then assessed motor function of KO (-/-) and WT mice by a tail suspension test. Both forelimb and hindlimb movements were significantly increased in 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 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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5934541PMC
http://dx.doi.org/10.5607/en.2018.27.2.103DOI Listing

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