title: Behavioral and metabolic characterization of heterozygous and homozygous POLG mutator mice.
abstract: 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.
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. ydai@bidmc.harvard.edu
authors.forename: Ying
authors.initials: Y
authors.lastname: Dai
authors.forename: Tomas
authors.initials: T
authors.lastname: Kiselak
authors.forename: Joanne
authors.initials: J
authors.lastname: Clark
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Clore
authors.forename: Kangni
authors.initials: K
authors.lastname: Zheng
authors.forename: Allen
authors.initials: A
authors.lastname: Cheng
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Kujoth
authors.forename: Tomas A
authors.initials: TA
authors.lastname: Prolla
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Maratos-Flier
authors.forename: David K
authors.initials: DK
authors.lastname: Simon
mesh_terms: D000818:Animals; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000378:metabolism*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics* / Q000378:metabolism*; D020233:Gait Disorders, Neurologic; D006579:Heterozygote; D006720:Homozygote; D006358:Hot Temperature; D051379:Mice; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism*; D009154:Mutation; D010101:Oxygen Consumption; D014793:Visual Cortex / Q000473:pathology
chemical_list: D004272:DNA, Mitochondrial; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C498803:Polg protein, mouse
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