Transgenic mice expressing human α-synuclein 1-103 fragment as a novel model of Parkinson’s disease
Parkinson’s disease (PD) is one of the most common neurodegenerative disorders. However, its cellular and molecular mechanisms still wrap in the mist. This is partially caused by the absence of an appropriate animal model mimicking sporadic PD that constitutes the majority of cases. Previously we reported that a cysteine protease, asparagine endopeptidase (AEP), is activated in an age-dependent manner, and cleaves α-synuclein in the brain of sporadic PD patients. The AEP-derived α-synuclein 1-103 fragment is required for the pathogenesis of PD. Thus, we designed and characterized a brand-new transgenic mouse line expressing α-synuclein 1-103 (designated N103 mice). This model shows an abundant accumulation of pathological α-synuclein in the central nervous system, loss of dopaminergic neurons in the substantia nigra, and progressive striatal synaptic degeneration. The N103 mice also manifest age-dependent PD-like behavioral impairments. Notably, the mice show weight loss and constipation, which are the common non-motor symptoms in PD. The RNA-sequencing analysis found that the transcriptomics pattern was extensively altered in N103 mice. In conclusion, the N103 mouse line is a candidate model of sporadic PD and may provide new insights into PD research.
Steps to reproduce
Transgenic mice expressing human α-synuclein 1-103 fragments were generated using fertilized egg injection. After behavioral tests, Molecular biology experiments, such as Western blots, IHC, IF, and RNA-sequencing were performed to characterize the pathological features of this mouse line.