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

Autor: Ekholm-Reed S; Department of Molecular Medicine, Scripps Research, 10550 North Torrey Pines Road, La Jolla, CA 92037 USA., Baker R; Department of Neuroscience, Scripps Research, 10550 North Torrey Pines Road, La Jolla, CA 92037 USA., Campos AR; 3Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 02037 USA., Stouffer D; Department of Molecular Medicine, Scripps Research, 10550 North Torrey Pines Road, La Jolla, CA 92037 USA., Henze M; Department of Molecular Medicine, Scripps Research, 10550 North Torrey Pines Road, La Jolla, CA 92037 USA., Wolf DA; 3Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 02037 USA., Loring JF; Department of Molecular Medicine, Scripps Research, 10550 North Torrey Pines Road, La Jolla, CA 92037 USA., Thomas EA; Department of Neuroscience, Scripps Research, 10550 North Torrey Pines Road, La Jolla, CA 92037 USA., Reed SI; Department of Molecular Medicine, Scripps Research, 10550 North Torrey Pines Road, La Jolla, CA 92037 USA.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2019 Apr 04; Vol. 2, pp. 125. Date of Electronic Publication: 2019 Apr 04 (Print Publication: 2019).
DOI: 10.1038/s42003-019-0366-x
Abstrakt: 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.
Competing Interests: The authors declare no competing interests.
Databáze: MEDLINE
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