Genetically engineered animal models of Parkinson's disease: From worm to rodent

Abstract

Parkinson's disease (PD) is a progressive neurological disorder characterised by aberrant accumulation of insoluble proteins, including alpha‐synuclein, and a loss of dopaminergic neurons in the substantia nigra. The extended neurodegeneration leads to a drop of striatal dopamine levels responsible for disabling motor and non‐motor impairments. Although the causes of the disease remain unclear, it is well accepted among the scientific community that the disorder may also have a genetic component. For that reason, the number of genetically engineered animal models has greatly increased over the past two decades, ranging from invertebrates to more complex organisms such as mice and rats. This trend is growing as new genetic variants associated with the disease are discovered. The EU Joint Programme – Neurodegenerative Disease Research (JPND) has promoted the creation of an online database aiming at summarising the different features of experimental models of Parkinson's disease. This review discusses available genetic models of PD and the extent to which they adequately mirror the human pathology and reflects on future development and uses of genetically engineered experimental models for the study of PD.

Menagerie: A text-mining tool to support animal-human translation in neurodegeneration research

“…Results confirm that the expected spectrum of vertebrate and invertebrate animal species and models used in PD research were captured [22,[68][69][70][71]. Additionally, the previously noted dominance of 6-OHDA and MPTP-associated toxic models [22] was reiterated.…”

Back and to the Future: From Neurotoxin‐Induced to Human Parkinson's Disease Models

“…The majority of transgenic mouse models focused on the expression of wild-type or mutant α-synuclein, and have been extensively reviewed elsewhere (Breger & Fuzzati Armentero, 2019;Koprich, Kalia, & Brotchie, 2017;Visanji et al, 2016). Most of these transgenic mice present very mild, if any, loss of dopaminergic neurons and many do not develop α-synuclein aggregation (Breger & Fuzzati Armentero, 2019).…”

“…The majority of transgenic mouse models focused on the expression of wild-type or mutant α-synuclein, and have been extensively reviewed elsewhere (Breger & Fuzzati Armentero, 2019;Koprich, Kalia, & Brotchie, 2017;Visanji et al, 2016). Most of these transgenic mice present very mild, if any, loss of dopaminergic neurons and many do not develop α-synuclein aggregation (Breger & Fuzzati Armentero, 2019). Interestingly, alanine to threonine substitution at position 53 (A53T) in human α-synuclein is associated with familial PD (Polymeropoulos et al, 1997), whereas mouse wild-type α-synuclein normally has threonine at position 53, which is not causing a PD phenotype.…”

Animal Models of Parkinson’s Disease: Are They Useful or Not?

“…The multitude of animal models available to us today is very broad, ranging from worms and flies to rodents and primates. While studies in worms and flies can be useful as tools to explore individual pathogenic pathways, and for high-throughput genetic screens, in particular [25] we need to resort to rodents and non-human primates in order to get closer to the human disease with Lewy body pathology and progressive nigrostriatal degeneration at the core. In many cases the rodent models have been developed, not to replicate all aspects of the disease, but to model selected, interacting pathways, such as mitochondrial dysfunction and damage, ␣-synuclein aggregation and spread, impaired degradation of misfolded proteins, or activation of the innate immune system [26,27].…”