In vivo models of Parkinson’s disease – Mammalian models

Genetic models

Alpha-synuclein

The alpha-synuclein gene (SNCA) is linked to a dominant type of familial form of Parkinon’s disease. Intracytoplasmic neuronal inclusions (Lewy Bodies) containing alpha-synuclein are a key cytopathological hallmark of the disease and today alpha-synuclein is a well established factor in the neurodegenerative process.

Alpha-synuclein is a 1440 amino acid protein, highly conserved among species and is ubiquitously expressed throughout the body.

Under physiological conditions alpha-synuclein is found in several oligomeric forms. Various phosphorylated and truncated physiological forms can also be observed.

Under pathological conditions the protein forms oligomer species that in turn form toxic proto-fibrils and amyloid fibrils.

Some familial forms of Parkinson’s disease show overexpression of the alpha-synuclein protein corresponding to duplication or triplication of the gene locus (SNCA) encoding  for the wild type protein.

Six unique point mutations have been identified in the SNCA gene in familial PD.

Because of the importance of (SNCA) in Parkinson’s disease pathology numerous mammalian models have been developed with either the full-length or truncated form of the protein, or point mutations of full length protein.

 

Species Alpha – synuclein Promoter Viral vector Neurodegeneration (Y/N) Link
Mouse hWT-syn PDGF na Y PDGF-hsynwt
Mouse hWT-syn Thy1 na Y Thy1-hsynwt
Mouse hWT-syn CaM-tTA na N CaM-tTA-hsynwt
Mouse hWT-syn PrP na N PrP-hsynwt
Mouse hWT-syn synuclein (PAC) na N PAC-hsynwt
Mouse hWT-syn TH (rat) na Y/N TH-hsynwt
Mouse hWT(1-120)-syn TH (rat) na Y TH-hsynwt(1-120)
Mouse hWT(1-119)syn ROSA26 na N ROSA26-hsynwt(1-119)
Mouse hA53T-syn CaM-tTA na Y CaM-tTA-hsynA53T
Mouse hA53T-syn synuclein (PAC) na N PAC-hsynA53T
Mouse hA53T-syn PrP na N PrP-hsynA53T
Mouse hA53T-syn Thy1 na N Thy1-hsynA53T
Mouse hA53T-syn PITX3 na Y PITX3-tTA-hsynA53T
Mouse hA53T-syn TH (rat) na N TH-hsynA53T
Mouse hA53T(1-130)-syn TH (rat) na Y TH-hsynA53T(1-130)
Mouse hA53T(1-119)-syn ROSA26 na N ROSA26-hsynA53T(1-119)
Mouse hA30P-syn Thy1 na N Thy1-hsynA30P
Mouse hA30P-syn synuclein (PAC) na N PAC-hsynA30P
Mouse hA30P-syn synuclein (BAC) na Y BAC-hsynA30P
Mouse hA30P-syn TH (rat) na N TH-hsynA30P
Mouse hA53T/A30P-syn TH (rat) na Y/N TH-hsynA53T-A30P
Mouse hE46K-syn PrP na N PrP-hsynE46K
Mouse hE46K(1-119)syn ROSA26 na N ROSA26-hsynE46K(1-119)
Rat hE46K-syn synuclein (BAC) na BAC-hsynE46K

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