title: Insight into Rett syndrome: MeCP2 levels display tissue- and cell-specific differences and correlate with neuronal maturation.
abstract: Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the methyl-CpG-binding protein 2 (MECP2) gene. Previous data have shown that MECP2 RNA is present in all mouse and human tissues tested, but the timing of expression and regional distribution have not been explored. We investigated the spatial and temporal distribution of the MeCP2 protein during mouse and human development. We found that in the adult mouse, MeCP2 is high in the brain, lung and spleen, lower in heart and kidney, and barely detectable in liver, stomach and small intestine. There was no obvious correlation between protein levels and RNA levels, suggesting that translation may be post-transcriptionally regulated by tissue-specific factors. The timing of MeCP2 expression in mouse and human correlated with the maturation of the central nervous system, with the ontogenetically older structures such as the spinal cord and brainstem becoming positive before newer structures such as the hippocampus and cerebral cortex. In the cortex, MeCP2 first appeared in the Cajal-Retzius cells, then in the neurons of the deeper, more mature cortical layers, and finally in the neurons of the more superficial layers. The MeCP2 protein was eventually present in a majority of neurons but was absent from glial cells. Our data suggest that MeCP2 may become abundant only once a neuron has reached a certain degree of maturity, and that this may explain some aspects of the RTT phenotype.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Mona D
authors.initials: MD
authors.lastname: Shahbazian
authors.forename: Barbara
authors.initials: B
authors.lastname: Antalffy
authors.forename: Dawna L
authors.initials: DL
authors.lastname: Armstrong
authors.forename: Huda Y
authors.initials: HY
authors.lastname: Zoghbi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D004622:Embryo, Mammalian / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism; D051783:Methyl-CpG-Binding Protein 2; D051379:Mice; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D012097:Repressor Proteins; D015518:Rett Syndrome / Q000209:etiology / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C497392:MECP2 protein, human; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D012097:Repressor Proteins