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Subtle changes

gene expression may account for the Rett syndrome phenotype.

Jonathan Weitzman(jonathanweitzman@hotmail.com)

Rett syndrome, a severe mental retardation disorder, is associated with mutations in the gene encoding methyl-CpG-binding protein-2. In the Early Edition of the Proceedings of the National Academy of Sciences, Matthew Tudor and colleagues describe transcriptional profiling analysis of brains from mice with a brain-specific deletion of the Mecp2 gene (PNAS, DOI:10.1073/pnas.242579699, November 11, 2002).

Mecp2-deficiency was predicted to result is dramatic changes in global gene expression, but this turns out not be the case. Statistical analysis of microarray data revealed few changes in gene expression, even in mutant mice displaying overt physiological symptoms. RNase protection experiments confirmed that a small number of genes change only slightly in mutant mouse brains.

Tudor et al. speculate that neurons may be sensitive to relatively subtle changes in gene expression, or that the Mecp2 deletion affects a small subset of cells in the brain, or that there is...

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