In vivo models of Parkinson’s disease – Mammalian models

Genetic models

LRRK2

The gene LRRK2 (Leucine-rich-repeat-kinase 2 gene, also known as dardarin) is located on the chromosome 12 (12q12) in the PARK8 locus. It is composed of 144 kb forming 53 exons (Gene ID: 120892). The LRRK2 protein is an unusually large kinase (2527 amino acids, 286 kDa) with Armadillo repeats (ARM), Ankyrin repeats (ANK), leucine-rich repeats (LRR), a Ras of complex proteins (Roc), a C-terminal of Roc (COR) and WD40 repeats.

Mutations in the LRRK2 gene have an autosomal dominant inheritance and are the most prevalent genetic causes of both familial and sporadic forms of Parkinson’s disease (PD). They are associated with a typical clinical features and a late-onset of the disease. Few mutations in the LRRK2 gene have been causally liked to PD (G2019S, R1441C, R1441G, R141H, I2020T, and Y1699C) and over 40 others have been identified as risk factors for the disease.

LRRK2 has been linked to various possible pathogenic mechanisms including α-synuclein and tau aggregation, inflammation, oxidative stress, mitochondrial, synaptic and autophagy-lysosomal dysfunctions.