Objective: To characterize the preclinical model parkinQ311X. Because the PARK2-associated disease in humans is characterized by juvenile onset and slow progression, in order to clarify whether the parkinQ311X model mirrors the human disease, it is important to define whether this model shows early dysfunction or neurodegeneration of SNpc dopaminergic neurons.

Background: Mutations in the PARK2 gene encoding the protein parkin cause autosomal recessive juvenile parkinsonism (ARJP) characterized by early loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The development and characterization of preclinical models is essential to clarify the neurodegeneration mechanisms and lay the groundwork for pharmacological treatments. ParkinQ311X is a transgenic mouse model expressing a mutant parkin variant, found in ARJP patients, selectively in dopaminergic neurons. Previous studies have shown that parkinQ311X mice exhibit dopamine neuron loss at 16 months of age.

Methods: We analysed dopaminergic neuron number in the SNpc of parkinQ311X mice and littermate controls at 1 and 6 months of age by stereological cell count. We also analysed by biochemical assays the levels of previously identified parkin substrates in SNpc and striatum.

Results: We found that parkinQ311X mice display an early dopaminergic neuron loss starting from 6 months of age. We also found that the expression of parkinQ311X leads to dysregulation of some parkin substrates.

Conclusions: These data suggest that this mouse line recapitulates some features of ARJP and provides an appropriate model for the study of the neurodegenerative mechanisms and the screening of neuroprotective drugs.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/characterization-of-the-preclinical-model-parkinq311x/