Transcriptional profiling of a mouse model for Rett syndrome reveals subtle transcriptional changes in the brain.
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.
Tudor
Matthew
M
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, 9 Cambridge Center, MA 02142, USA.
Akbarian
Schahram
S
Chen
Richard Z
RZ
Jaenisch
Rudolf
R
D000367:Age Factors; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D051783:Methyl-CpG-Binding Protein 2; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D023421:Models, Animal; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D016548:Prosencephalon / Q000378:metabolism; D012097:Repressor Proteins; D015518:Rett Syndrome / Q000235:genetics*; D012260:Ribonucleases; D014158:Transcription, Genetic
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; D012260:Ribonucleases