Reducing Mcl-1 gene dosage induces dopaminergic neuronal loss and motor impairments in Park2 knockout mice. View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-12

AUTHORS

Susanna Ekholm-Reed, Robert Baker, Alexandre R Campos, David Stouffer, Martha Henze, Dieter A Wolf, Jeanne F Loring, Elizabeth A Thomas, Steven I Reed

ABSTRACT

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. More... »

PAGES

125

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s42003-019-0366-x

DOI

http://dx.doi.org/10.1038/s42003-019-0366-x

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1113237901

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30963113


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