Transcriptional profiling of a mouse model for Rett syndrome reveals subtle transcriptional changes in the brain.
Proc Natl Acad Sci U S A
; 99(24): 15536-41, 2002 Nov 26.
Article
em En
| MEDLINE
| ID: mdl-12432090
The Mecp2 gene has been shown to be mutated in most cases of human Rett syndrome, and mouse models deleted for the ortholog have been generated. Lineage-specific deletion of the gene indicated that the Rett-like phenotype is caused by Mecp2 deficiency in neurons. Biochemical evidence suggests that Mecp2 acts as a global transcriptional repressor, predicting that mutant mice should have genome-wide transcriptional deregulation. We tested this hypothesis by comparing global gene expression in wild-type and Mecp2 mutant mice. The results of numerous microarray analyses revealed no dramatic changes in transcription even in mice displaying overt disease symptoms, although statistical power analyses of the data indicated that even a small number of relatively subtle changes in transcription would have been detected if present. However, a classifier consisting of a combined small set of genes was able to distinguish between mutant and wild-type samples with high accuracy. This result suggests that Mecp2 deficiency leads to subtle gene expression changes in mutant brains which may be associated with the phenotypic changes observed.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
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Transcrição Gênica
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Encéfalo
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Proteínas Cromossômicas não Histona
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Síndrome de Rett
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Perfilação da Expressão Gênica
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Proteínas de Ligação a DNA
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Proteínas do Tecido Nervoso
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
Estados Unidos