Development

Neuronal Maturation

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Science  30 Apr 2004:
Vol. 304, Issue 5671, pp. 653
DOI: 10.1126/science.304.5671.653a

Rett syndrome is a childhood neurodevelopmental disorder that occurs primarily in females and is characterized by progressive autism and mental retardation. Mutations in MECP2, a gene that encodes a methyl-CpG-binding protein, are associated with about 80% of all cases. The MeCP2 protein is highly expressed in postnatal brain neurons, mediates transcriptional silencing by recruiting chromatin-modifying factors, and is thought to regulate genes involved in synaptic activity and neuronal maturation.

Mutant mice lacking functional MeCP2 exhibit phenotypes similar to those of Rett syndrome patients, including decreased head growth and smaller and more densely packed neurons. Luikenhius et al. demonstrate that expression of a Mecp2 transgene in postmitotic brain neurons of these mutant mice restores a normal phenotype; however, overexpression resulted in severe neural dysfunction, suggesting that the amount of MeCP2 may be tightly controlled. Carro et al. have identified a Xenopus protein that binds to human MeCP2 and increases its half-life when expressed in a human cell line. This protein resembles serine protease inhibitors and might furnish a mechanistic clue because some Rett syndrome patients harbor deletions in MeCP2 that yield proteins of reduced stability. — LDC

Proc. Natl. Acad. Sci. U.S.A. 101, 6033 (2004); J. Biol. Chem. 10.1074/jbc.M402571200 (2004).

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