Yoon, Yeojun Park, Hasang Kim, Sangyeon Nguyen, Phuong T. Hyeon, Seung Jae Chung, Sooyoung Im, Hyeonjoo Lee, Junghee Lee, Sean Bong Ryu, Hoon 2024-01-19T23:02:51Z 2024-01-19T23:02:51Z 2021-09-03 2018-04 1226-2560 https://pubs.kist.re.kr/handle/201004/121537 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. English KOREAN SOC BRAIN & NEURAL SCIENCE, KOREAN SOC NEURODEGENERATIVE DISEASE AMYOTROPHIC-LATERAL-SCLEROSIS FRONTOTEMPORAL LOBAR DEGENERATION EWING SARCOMA PROTEIN FET PROTEINS TET FAMILY FUSION DISEASE TUMORS TRANSLOCATION MUTATIONS Genetic Ablation of EWS RNA Binding Protein 1 (EWSR1) Leads to Neuroanatomical Changes and Motor Dysfunction in Mice Article 10.5607/en.2018.27.2.103 1 EXPERIMENTAL NEUROBIOLOGY, v.27, no.2, pp.103 - 111 EXPERIMENTAL NEUROBIOLOGY 27 2 103 111 scie scopus kci ART002345424 000433039400004 2-s2.0-85046420113 Medicine, Research & Experimental Neurosciences Research & Experimental Medicine Neurosciences & Neurology Article AMYOTROPHIC-LATERAL-SCLEROSIS FRONTOTEMPORAL LOBAR DEGENERATION EWING SARCOMA PROTEIN FET PROTEINS TET FAMILY FUSION DISEASE TUMORS TRANSLOCATION MUTATIONS EWSR1 central nervous system (CNS) neuron dopamine DARPP-32 motor function