Reducing Mcl-1 gene dosage induces dopaminergic neuronal loss and motor impairments in Park2 knockout mice.
Commun Biol
; 2: 125, 2019.
Article
en En
| MEDLINE
| ID: mdl-30963113
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Dosificación de Gen
/
Ubiquitina-Proteína Ligasas
/
Técnicas de Inactivación de Genes
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Neuronas Dopaminérgicas
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Proteína 1 de la Secuencia de Leucemia de Células Mieloides
/
Actividad Motora
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Commun Biol
Año:
2019
Tipo del documento:
Article