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.

SpeciesLRRK2PromoterViral vectorNeurodegenerationLink
MousehWTCamKIIa-TetOffnaNCaM-tTA-hLRRK2-WT
MousehWTCMVE/PDGFnaNCMVE/PDGF-hLRRK2-WT
MousehWThLRRK2(BAC)naNBAC-hLRRK2-WT-1
MousehWTPitx3-tTAnaNPitx3-TTA-hLRRK2-WT
MousehWTThy1naNThy1-hLRRK2-WT
MousehWTThy1.2naNThy1.2-hLRRK2-WT
MousemWTmLRRK2 (BAC)naNBAC-mLRRK2-WT
MousehG2019SCaM-tTAnaNCaM-tTA-hLRRK2-G2019S
MousehG2019SCMVE/PDGFnaY/NCMVE/PDGF-hLRRK2-G2019S
MousehG2019ShLRRK2 (BAC)naNBAC-hLRRK2-G2019S
MousehG2019SPitx3-tTAnaNPitx3-tTA-hLRRK2-G2019S
MousehG2019SThy1naNThy1-hLRRK2-G2019S
MousehG2019SThy1.2naNThy1.2-hLRRK2-G2019S
MousemG2019SmLRRK2 (Knock-In)naNmLRRK2-G2019S
MousemG2019SmLRRK2 (BAC)naNoBAC-mLRRK2-G2019S
MousehR1441CCMVE/PDGFnaVariableCMVE/PDGF-hLRRK2-R1441C
MousehR1441GhLRRK2 (BAC)naNBAC-hLRRK2-R1441G
MouseKOKOnaNLRRK2-KO-Mouse
RathWTCAG-tTA/TRE-miniCMVnaNtTA-hLRRK2-WT-Rat
RathWThLRRK2 (BAC)naNBAC-huLRRK2-WT
RathG2019SCAG-tTA/TRE-miniCMVnaNtTA-hLRRK2-G2019S-Rat
RathG2019ShLRRK2 (BAC)naNBAC-hLRRK2-G2019S-Rat
RathG2019Ssynapsin-1AdenovirusVariableAdV-hLRRK2-G2019S
RathR1441ChLRRK2 (BAC)naNBAC-hLRRK2-R1441C-Rat
RathR1441GhLRRK2 (BAC)naNBAC-hLRRK2-R1441G-Rat
RatKOKOnaNLRRK2-KO-Rat