Gene Expression Analysis Exposes Mitochondrial Abnormalities in a Mouse Model of Rett Syndrome

Skirmantas Kriaucionis, Andrew W. J. Paterson, John Curtis, Jacqueline Guy, Nikki MacLeod, Adrian Bird

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)5033-5042
JournalMolecular and Cellular Biology
Volume26
Issue number13
DOIs
Publication statusPublished - 2006

Fingerprint

Dive into the research topics of 'Gene Expression Analysis Exposes Mitochondrial Abnormalities in a Mouse Model of Rett Syndrome'. Together they form a unique fingerprint.

Cite this