1. Absence of Motor Impairments or Pathological Changes in TMEM230 Knockout Rats
- Author
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Zhang, Wenjuan, Peng, Hao, Yang, Daihe, Song, Guohua, He, Juan, Zhou, Yun, Huang, Cao, Huang, Bo, Zhang, Wenjuan, Peng, Hao, Yang, Daihe, Song, Guohua, He, Juan, Zhou, Yun, Huang, Cao, and Huang, Bo
- Abstract
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.
- Published
- 2024