Behavioral and metabolic characterization of heterozygous and homozygous POLG mutator mice

The mitochondrial DNA (mtDNA) polymerase γ (POLG) mutator mice provide the first experimental evidence that high levels of somatic mtDNA mutations can be functionally significant. Here we report that older homozygous, but not heterozygous, POLG mice show significant reductions in striatal dopaminerg...

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Bibliographic Details
Published in:Mitochondrion 2013-07, Vol.13 (4), p.282-291
Main Authors: Dai, Ying, Kiselak, Tomas, Clark, Joanne, Clore, Elizabeth, Zheng, Kangni, Cheng, Allen, Kujoth, Gregory C, Prolla, Tomas A, Maratos-Flier, Eleftheria, Simon, David K
Format: Article
Language:English
Subjects:
Animals
DNA Polymerase gamma
DNA, Mitochondrial - metabolism
DNA-Directed DNA Polymerase - genetics
DNA-Directed DNA Polymerase - metabolism
Gait Disorders, Neurologic
Heterozygote
Homozygote
Hot Temperature
Mice
Mitochondria - enzymology
Mitochondria - metabolism
Mutation
Oxygen Consumption
Visual Cortex - pathology
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Summary:The mitochondrial DNA (mtDNA) polymerase γ (POLG) mutator mice provide the first experimental evidence that high levels of somatic mtDNA mutations can be functionally significant. Here we report that older homozygous, but not heterozygous, POLG mice show significant reductions in striatal dopaminergic terminals as well as deficits in motor function. However, resting oxygen consumption, heat production, mtDNA content and mitochondrial electron transport chain activities are significantly decreased at older ages in both homozygous and heterozygous mice. These results indicate that high levels of somatic mtDNA mutations can contribute to dopaminergic dysfunction and to behavioral and metabolic deficits.
ISSN:1567-7249
1872-8278
DOI:10.1016/j.mito.2013.03.006