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Reducing Mcl-1 gene dosage induces dopaminergic neuronal loss and motor impairments in Park2 knockout mice
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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449387/ https://www.ncbi.nlm.nih.gov/pubmed/30963113 http://dx.doi.org/10.1038/s42003-019-0366-x |
Sumario: | 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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