Absence of motor impairments or pathological changes in TMEM230 knockout rats.

Autor: Zhang W; Innovation Research Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Changqing District, Shandong, China., Peng H; Department of Neurosurgery, The Second People's Hospital of Hainan Province, Hainan, China; Department of Neurosurgery, Hainan General Hospital, Hainan Medical University, Hainan, China., Yang D; Department of Anesthesiology, the Affiliated Second People's Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou 350003, China., Song G; Laboratory Animal Center, Shanxi Medical University, No 56, Xinjian South Rd, Taiyuan 030001, China., He J; Hospital of Integrated Traditional Chinese and Western Medicine in Shanxi Province, Taiyuan, Shanxi 030012, China., Zhou Y; Hospital of Integrated Traditional Chinese and Western Medicine in Shanxi Province, Taiyuan, Shanxi 030012, China., Huang C; Department of Pathology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA. Electronic address: huangc57@mail.sysu.edu.cn., Huang B; Hospital of Integrated Traditional Chinese and Western Medicine in Shanxi Province, Taiyuan, Shanxi 030012, China; Laboratory Animal Center, Shanxi Provincial People's Hospital, Taiyuan, Shanxi, China; Medical Sciences, UCSI University, Kuala Lumpur 56000, Malaysia. Electronic address: langlang@sxmu.edu.cn.
Jazyk: angličtina
Zdroj: Neuroscience letters [Neurosci Lett] 2024 Aug 10; Vol. 837, pp. 137921. Date of Electronic Publication: 2024 Aug 04.
DOI: 10.1016/j.neulet.2024.137921
Abstrakt: Parkinson's disease (PD), which is the second most common neurodegenerative disorder, is characterized by progressive movement impairment and loss of midbrain dopaminergic neurons in the substantia nigra. Although mutations in TMEM230 are linked to familial PD, the pathogenic mechanism underlying TMEM230-associated PD remains to be elucidated. To explore the effect of TMEM230 depletion in vivo, we created TMEM230 knockout rats using CRISPR-Cas9 technology. TMEM230 knockout rats did not exhibit any core features of PD, including impaired motor function, loss of dopaminergic neurons in the substantia nigra, or altered expression of proteins related to autophagy, the Rab family, or vesicular trafficking. In addition, no glial reactions were observed in TMEM230 knockout rats. These results indicate that depletion of TMEM230 may not lead to dopaminergic neuron degeneration in rats, further supporting that PD-associated TMEM230 mutations lead to dopaminergic neuron death by gain-of-toxic function.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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