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Mol Cell Biol. 2006 Jul;26(13):5033-42.

Gene expression analysis exposes mitochondrial abnormalities in a mouse model of Rett syndrome.

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  • 1The Wellcome Trust Centre for Cell Biology, University of Edinburgh, Michael Swann Building, The King's Buildings, Edinburgh EH9 3JR, United Kingdom.

Abstract

Rett syndrome (RTT) is a severe neurological disorder caused by mutations in the X-linked MECP2 gene, which encodes a methyl-CpG binding transcriptional repressor. Using the Mecp2-null mouse (an animal model for RTT) and differential display, we found that mice with neurological symptoms overexpress the nuclear gene for ubiquinol-cytochrome c reductase core protein 1 (Uqcrc1). Chromatin immunoprecipitation demonstrated that MeCP2 interacts with the Uqcrc1 promoter. Uqcrc1 encodes a subunit of mitochondrial respiratory complex III, and isolated mitochondria from the Mecp2-null brain showed elevated respiration rates associated with respiratory complex III and an overall reduction in coupling. A causal link between Uqcrc1 gene overexpression and enhanced complex III activity was established in neuroblastoma cells. Our findings raise the possibility that mitochondrial dysfunction contributes to pathology of the Mecp2-null mouse and may contribute to the long-known resemblance between Rett syndrome and certain mitochondrial disorders.

PMID:
16782889
PMCID:
PMC1489175
DOI:
10.1128/MCB.01665-05
[PubMed - indexed for MEDLINE]
Free PMC Article
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