(R1441C) LRRK2 induces the degeneration of SN dopaminergic neurons and alters the expression of genes regulating neuronal survival in a transgenic mouse model

Yi Hsin Weng, Chu Yu Chen, Kun Jun Lin, Ying Ling Chen, Tu Hsueh Yeh, Ing Tsung Hsiao, Ing Jou Chen, Chin Song Lu, Hung Li Wang

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Mutation of leucine-rich repeat kinase 2 (LRRK2) is the most common genetic cause of both familial and sporadic Parkinson's disease (PD) cases. Several mutations in LRRK2 gene were reported in PD patients. R1441 is the second most frequent site of LRRK2 mutation. We generated (R1441C) LRRK2 transgenic mice that displayed motor deficits at the age of 16. months. Compared with wild-type mice, 16-month-old (R1441C) LRRK2 mice exhibited a significant reduction in the number of substantia nigra (SN) dopaminergic neurons. To elucidate molecular pathogenic pathways involved in (R1441C) LRRK2-induced death of SN dopaminergic neurons, we performed microarray analysis to visualize altered mRNA expressions in the SN of (R1441C) LRRK2 mouse. In the SN of (R1441C) LRRK2 transgenic mouse, the mRNA expression of three genes that promote cell death was upregulated, while the mRNA expression of seven genes that contribute to neurogenesis/neuroprotection was significantly downregulated. Our results suggest that altered expression of these genes involved in regulating neuronal survival may contribute to the pathogenesis of (R1441C) LRRK2-induced PD.

Original languageEnglish
Pages (from-to)104-115
Number of pages12
JournalExperimental Neurology
Volume275
DOIs
Publication statusPublished - Jan 1 2016
Externally publishedYes

Fingerprint

Dopaminergic Neurons
Substantia Nigra
Leucine
Transgenic Mice
Phosphotransferases
Gene Expression
Parkinson Disease
Messenger RNA
Mutation
Neurogenesis
Microarray Analysis
Cell Death
Down-Regulation
Genes

Keywords

  • (R1441C) LRRK2
  • Microarray
  • Parkinson's disease
  • Transgenic mice

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience
  • Medicine(all)

Cite this

(R1441C) LRRK2 induces the degeneration of SN dopaminergic neurons and alters the expression of genes regulating neuronal survival in a transgenic mouse model. / Weng, Yi Hsin; Chen, Chu Yu; Lin, Kun Jun; Chen, Ying Ling; Yeh, Tu Hsueh; Hsiao, Ing Tsung; Chen, Ing Jou; Lu, Chin Song; Wang, Hung Li.

In: Experimental Neurology, Vol. 275, 01.01.2016, p. 104-115.

Research output: Contribution to journalArticle

Weng, Yi Hsin ; Chen, Chu Yu ; Lin, Kun Jun ; Chen, Ying Ling ; Yeh, Tu Hsueh ; Hsiao, Ing Tsung ; Chen, Ing Jou ; Lu, Chin Song ; Wang, Hung Li. / (R1441C) LRRK2 induces the degeneration of SN dopaminergic neurons and alters the expression of genes regulating neuronal survival in a transgenic mouse model. In: Experimental Neurology. 2016 ; Vol. 275. pp. 104-115.
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