Introducing PIGMO, a novel PIGmented MOuse model of Parkinson’s disease (V1)

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ABSTRACT There is a pressing need for the development, characterization, and standardization of animal models of Parkinson’s disease (PD) that properly mimic the cardinal features of this disorder, comprising both the motor phenotype and neuropathological signatures. In the past few years, animal modeling has moved from neurotoxin-based approaches toward viral vectors carrying a given genetic payload of interest. Here, to induce pigmentation of the mouse brain upon systemic delivery, we took advantage of a modified adeno-associated viral vector capsid engineered to bypass the blood-brain barrier and coding for the human tyrosinase gene (AAV9-P31-hTyr). Obtained results revealed an ongoing pigmentation of catecholaminergic centers related to the pathophysiology of PD, such as the substantia nigra pars compacta, ventral tegmental area, and locus coeruleus. Moreover, pigmented dopaminergic neurons exhibited Lewy body-like intracytoplasmic inclusions, a progressive nigrostriatal degeneration, and a time-dependent PD motor phenotype. The bilateral pigmented mouse model of PD generated this way is highly reproducible, does not require stereotaxic surgery for viral vector deliveries, and opens unprecedented possibilities for preclinical testing of therapeutic candidates designed to reduce disease progression rates.

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