The M83 A53T α-synuclein transgenic mouse model is one of the most widely used transgenic mouse models for studying synucleinopathies and evaluating therapeutics targeting α-synuclein-driven neurodegeneration. 

Mutations, duplications, and triplications in the SNCA gene, including A53T, A30P, and E46K variants, are linked to autosomal dominant Parkinson’s disease and related synucleinopathies. The M83 mouse model overexpresses the human A53T mutant α-synuclein protein under the mouse prion protein (PrP) promoter, resulting in widespread neuronal expression throughout the central nervous system. 

α-Synuclein is a presynaptic neuronal protein centrally involved in Parkinson’s disease pathogenesis and Lewy body formation. The M83 model recapitulates key hallmarks of progressive α-synucleinopathy, including age-dependent aggregation of pathological α-synuclein, neuroinflammation, and motor dysfunction. The mouse model has been shown in the literature to have early onset fine motor and sensorimotor behavioural impairments before robust motor dysfunction is observed (Paumier et al., 2013). 

At InnoSer, the A53T alpha-synuclein mouse model is used across both spontaneous disease progression studies and accelerated α-synuclein seeding paradigms using (human and/or mouse) pre-formed fibrils (PFFs) or patient brain extracts, enabling flexible and translationally relevant study designs.