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Open AccessArticle

DRG2 Deficient Mice Exhibit Impaired Motor Behaviors with Reduced Striatal Dopamine Release

1
Research Division and Brain Research Core Facilities of Korea Brain Research Institute, Daegu 41068, Korea
2
Department of Biological Sciences, University of Ulsan, Ulsan 44610, Korea
3
Dementia Research Group and Neurodegenerative Disease Group, Korea Brain Research Institute, Daegu 41068, Korea
4
Department of Brain and Cognitive Science, DGIST, Daegu 42988, Korea
5
School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Korea
6
College of Korean Medicine, Daegu Haany University, Daegu 42158, Korea
7
Department of Psychology, Korea University, Seoul 02841, Korea
8
School of Exercise and Sport Science, University of Ulsan, Ulsan 44610, Korea
9
Department of Anatomy, College of Medicine, Korea University, Seoul 02841, Korea
10
Gwangju Center, Korea Basic Science Institute (KBSI), Gwangju 61886, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(1), 60; https://doi.org/10.3390/ijms21010060
Received: 11 November 2019 / Revised: 17 December 2019 / Accepted: 18 December 2019 / Published: 20 December 2019
(This article belongs to the Special Issue Molecular Mechanisms of Neural Circuit Development and Regeneration)
Developmentally regulated GTP-binding protein 2 (DRG2) was first identified in the central nervous system of mice. However, the physiological function of DRG2 in the brain remains largely unknown. Here, we demonstrated that knocking out DRG2 impairs the function of dopamine neurons in mice. DRG2 was strongly expressed in the neurons of the dopaminergic system such as those in the striatum (Str), ventral tegmental area (VTA), and substantia nigra (SN), and on neuronal cell bodies in high-density regions such as the hippocampus (HIP), cerebellum, and cerebral cortex in the mouse brain. DRG2 knockout (KO) mice displayed defects in motor function in motor coordination and rotarod tests and increased anxiety. However, unexpectedly, DRG2 depletion did not affect the dopamine (DA) neuron population in the SN, Str, or VTA region or dopamine synthesis in the Str region. We further demonstrated that dopamine release was significantly diminished in the Str region of DRG2 KO mice and that treatment of DRG2 KO mice with l-3,4-dihydroxyphenylalanine (L-DOPA), a dopamine precursor, rescued the behavioral motor deficiency in DRG2 KO mice as observed with the rotarod test. This is the first report to identify DRG2 as a key regulator of dopamine release from dopamine neurons in the mouse brain. View Full-Text
Keywords: Developmentally regulated GTP-binding protein 2 (DRG2); Dopamine release; Motor deficiency; Dopaminergic neurons; Motor coordination; Striatum Developmentally regulated GTP-binding protein 2 (DRG2); Dopamine release; Motor deficiency; Dopaminergic neurons; Motor coordination; Striatum
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MDPI and ACS Style

Lim, H.R.; Vo, M.-T.; Kim, D.J.; Lee, U.H.; Yoon, J.H.; Kim, H.-J.; Kim, J.; Kim, S.R.; Lee, J.Y.; Yang, C.H.; Kim, H.Y.; Choi, J.-S.; Kim, K.; Yang, E.; Kim, H.; Lee, S.; Lee, B.J.; Kim, K.; Park, J.W.; Ha, C.M. DRG2 Deficient Mice Exhibit Impaired Motor Behaviors with Reduced Striatal Dopamine Release. Int. J. Mol. Sci. 2020, 21, 60. https://doi.org/10.3390/ijms21010060

AMA Style

Lim HR, Vo M-T, Kim DJ, Lee UH, Yoon JH, Kim H-J, Kim J, Kim SR, Lee JY, Yang CH, Kim HY, Choi J-S, Kim K, Yang E, Kim H, Lee S, Lee BJ, Kim K, Park JW, Ha CM. DRG2 Deficient Mice Exhibit Impaired Motor Behaviors with Reduced Striatal Dopamine Release. International Journal of Molecular Sciences. 2020; 21(1):60. https://doi.org/10.3390/ijms21010060

Chicago/Turabian Style

Lim, Hye R.; Vo, Mai-Tram; Kim, Dong J.; Lee, Unn H.; Yoon, Jong H.; Kim, Hyung-Jun; Kim, Jeongah; Kim, Sang R.; Lee, Jun Y.; Yang, Chae H.; Kim, Hee Y.; Choi, June-Seek; Kim, Kijeong; Yang, Esther; Kim, Hyun; Lee, Seongsoo; Lee, Byung J.; Kim, Kyungjin; Park, Jeong W.; Ha, Chang M. 2020. "DRG2 Deficient Mice Exhibit Impaired Motor Behaviors with Reduced Striatal Dopamine Release" Int. J. Mol. Sci. 21, no. 1: 60. https://doi.org/10.3390/ijms21010060

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