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.

Species LRRK2 Promoter Viral vector Neurodegeneration Link
Mouse hWT CamKIIa-TetOff na N CaM-tTA-hLRRK2-WT
Mouse hWT CMVE/PDGF na N CMVE/PDGF-hLRRK2-WT
Mouse hWT hLRRK2(BAC) na N BAC-hLRRK2-WT-1
Mouse hWT Pitx3-tTA na N Pitx3-TTA-hLRRK2-WT
Mouse hWT Thy1 na N Thy1-hLRRK2-WT
Mouse hWT Thy1.2 na N Thy1.2-hLRRK2-WT
Mouse mWT mLRRK2 (BAC) na N BAC-mLRRK2-WT
Mouse hG2019S CaM-tTA na N CaM-tTA-hLRRK2-G2019S
Mouse hG2019S CMVE/PDGF na Y/N CMVE/PDGF-hLRRK2-G2019S
Mouse hG2019S hLRRK2 (BAC) na N BAC-hLRRK2-G2019S
Mouse hG2019S Pitx3-tTA na N Pitx3-tTA-hLRRK2-G2019S
Mouse hG2019S Thy1 na N Thy1-hLRRK2-G2019S
Mouse hG2019S Thy1.2 na N Thy1.2-hLRRK2-G2019S
Mouse mG2019S mLRRK2 (Knock-In) na N mLRRK2-G2019S
Mouse mG2019S mLRRK2 (BAC) na No BAC-mLRRK2-G2019S
Mouse hR1441C CMVE/PDGF na Variable CMVE/PDGF-hLRRK2-R1441C
Mouse hR1441G hLRRK2 (BAC) na N BAC-hLRRK2-R1441G
Mouse KO KO na N LRRK2-KO-Mouse
Rat hWT CAG-tTA/TRE-miniCMV na N tTA-hLRRK2-WT-Rat
Rat hWT hLRRK2 (BAC) na N BAC-huLRRK2-WT
Rat hG2019S CAG-tTA/TRE-miniCMV na N tTA-hLRRK2-G2019S-Rat
Rat hG2019S hLRRK2 (BAC) na N BAC-hLRRK2-G2019S-Rat
Rat hG2019S synapsin-1 Adenovirus Variable AdV-hLRRK2-G2019S
Rat hR1441C hLRRK2 (BAC) na N BAC-hLRRK2-R1441C-Rat
Rat hR1441G hLRRK2 (BAC) na N BAC-hLRRK2-R1441G-Rat
Rat KO KO na N LRRK2-KO-Rat