Gene expression analysis exposes mitochondrial abnormalities in a mouse model of Rett syndrome.
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...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
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2006
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| _version_ | 1826278642460655616 |
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| author | Kriaucionis, S Paterson, A Curtis, J Guy, J Macleod, N Bird, A |
| author_facet | Kriaucionis, S Paterson, A Curtis, J Guy, J Macleod, N Bird, A |
| author_sort | Kriaucionis, S |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T23:46:58Z |
| format | Journal article |
| id | oxford-uuid:71439b58-458a-4b8a-ba69-1e42c3fbe4b2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:46:58Z |
| publishDate | 2006 |
| record_format | dspace |
| spelling | oxford-uuid:71439b58-458a-4b8a-ba69-1e42c3fbe4b22022-03-26T19:42:28ZGene expression analysis exposes mitochondrial abnormalities in a mouse model of Rett syndrome.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:71439b58-458a-4b8a-ba69-1e42c3fbe4b2EnglishSymplectic Elements at Oxford2006Kriaucionis, SPaterson, ACurtis, JGuy, JMacleod, NBird, ARett 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. |
| spellingShingle | Kriaucionis, S Paterson, A Curtis, J Guy, J Macleod, N Bird, A Gene expression analysis exposes mitochondrial abnormalities in a mouse model of Rett syndrome. |
| title | Gene expression analysis exposes mitochondrial abnormalities in a mouse model of Rett syndrome. |
| title_full | Gene expression analysis exposes mitochondrial abnormalities in a mouse model of Rett syndrome. |
| title_fullStr | Gene expression analysis exposes mitochondrial abnormalities in a mouse model of Rett syndrome. |
| title_full_unstemmed | Gene expression analysis exposes mitochondrial abnormalities in a mouse model of Rett syndrome. |
| title_short | Gene expression analysis exposes mitochondrial abnormalities in a mouse model of Rett syndrome. |
| title_sort | gene expression analysis exposes mitochondrial abnormalities in a mouse model of rett syndrome |
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