Behavioral and metabolic characterization of heterozygous and homozygous POLG mutator mice

被引：29

作者：

Dai, Ying ^{[1
]}

Kiselak, Tomas ^{[1
]}

Clark, Joanne ^{[1
]}

Clore, Elizabeth ^{[1
]}

Zheng, Kangni ^{[1
]}

Cheng, Allen ^{[2
]}

Kujoth, Gregory C. ^{[3
]}

Prolla, Tomas A. ^{[3
]}

Maratos-Flier, Eleftheria ^{[4
]}

Simon, David K. ^{[1
]}

机构：

[1] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Neurol, Sch Med, Boston, MA 02215 USA

[2] Harvard Univ, Sch Med, MD PhD Program, Boston, MA 02115 USA

[3] Univ Wisconsin, Dept Genet & Med Genet, Madison, WI 53706 USA

[4] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Endocrinol, Dept Med,Med Sch, Boston, MA 02215 USA

来源：

MITOCHONDRION | 2013年 / 13卷 / 04期

关键词：

mtDNA polymerase gamma; mtDNA mutation; Parkinson's disease; Dopamine; Behavioral deficits; Metabolic deficits; MITOCHONDRIAL-DNA MUTATIONS; PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; HUMAN SUBSTANTIA-NIGRA; PARKINSONS-DISEASE; DOPAMINERGIC-NEURONS; POINT MUTATIONS; MTDNA MUTATIONS; COMPLEX-I; DELETIONS; ABNORMALITIES;

D O I：

10.1016/j.mito.2013.03.006

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

The mitochondrial DNA (mtDNA) polymerase (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. (c) 2013 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

引用

页码：282 / 291

页数：10

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