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Publication : Reducing <i>Mcl-1</i> gene dosage induces dopaminergic neuronal loss and motor impairments in <i>Park2</i> knockout mice.

First Author  Ekholm-Reed S Year  2019
Journal  Commun Biol Volume  2
Pages  125 PubMed ID  30963113
Mgi Jnum  J:278038 Mgi Id  MGI:6356095
Doi  10.1038/s42003-019-0366-x Citation  Ekholm-Reed S, et al. (2019) Reducing Mcl-1 gene dosage induces dopaminergic neuronal loss and motor impairments in Park2 knockout mice. Commun Biol 2:125
abstractText  Mutations in the PARK2 gene are associated with early onset Parkinsonism. The Park2 (-/-) mouse, however, does not exhibit neurodegeneration or other Parkinson's disease (PD) phenotypes. Previously, we discovered that translation of Mcl-1, a pro-survival factor, is upregulated in the Park2 (-/-) mouse, suggesting a compensatory mechanism during development. Here we generated the Park2 (-/-) Mcl-1 (+/-) mouse and show that by reducing Mcl-1 gene dosage by 50%, the Park2 (-/-) genotype is sensitized, conferring both dopaminergic neuron loss and motor impairments. We propose that this murine model could be a useful tool for dissecting PD etiology and developing treatment strategies against this neurodegenerative disease.
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