Dopaminergic Neuron-Specific Autophagy-Deficient Mice

Abstract

None of the current genetic Parkinson’s disease (PD) models in mouse recapitulates all features of PD. Additionally, only a few of these models develop mild dopamine (DA) neurodegeneration. And the most parsimonious explanation for the lack of DA neurodegeneration in genetic PD models is a compensatory mechanism that results from adaptive changes during development, making it hard to observe the degenerative phenotype over the life span of mice. Here, we characterize DA neuron-specific autophagy-deficient mice and provide in vivo evidence for Lewy body formation. Atg7-deficient mice demonstrate typical Lewy pathology, including endogenous synuclein and neuronal loss, which resembles PD. Furthermore DA levels are affected by dopaminergic neuronal loss. The age-related motor dysfunction and pathology in DA neurons suggest that impairment of autophagy is a potential mechanism underlying the pathology of PD.