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 140 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.

 

SpeciesAlpha – synucleinPromoterViral vectorNeurodegeneration (Y/N)Link
MousehWT-synPDGFnaYPDGF-hsynwt
MousehWT-synThy1naYThy1-hsynwt
MousehWT-synCaM-tTAnaNCaM-tTA-hsynwt
MousehWT-synPrPnaNPrP-hsynwt
MousehWT-synsynuclein (PAC)naNPAC-hsynwt
MousehWT-synTH (rat)naY/NTH-hsynwt
MousehWT(1-120)-synTH (rat)naYTH-hsynwt(1-120)
MousehWT(1-119)synROSA26naNROSA26-hsynwt(1-119)
MousehA53T-synCaM-tTAnaYCaM-tTA-hsynA53T
MousehA53T-synsynuclein (PAC)naNPAC-hsynA53T
MousehA53T-synPrPnaYPrP-hsynA53T
MousehA53T-synThy1naNThy1-hsynA53T
MousehA53T-synPITX3naYPITX3-tTA-hsynA53T
MousehA53T-synTH (rat)naNTH-hsynA53T
MousehA53T(1-130)-synTH (rat)naYTH-hsynA53T(1-130)
MousehA53T(1-119)-synROSA26naNROSA26-hsynA53T(1-119)
MousehA30P-synThy1naNThy1-hsynA30P
MousehA30P-synsynuclein (PAC)naNPAC-hsynA30P
MousehA30P-synsynuclein (BAC)naYBAC-hsynA30P
MousehA30P-synTH (rat)naNTH-hsynA30P
MousehA53T/A30P-synTH (rat)naY/NTH-hsynA53T-A30P
MousehE46K-synPrPnaNPrP-hsynE46K
MousehE46K(1-119)synROSA26naNROSA26-hsynE46K(1-119)
RathE46K-synsynuclein (BAC)na NBAC-hsynE46K

Updated 20/07/2018

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