MeCP2 mutant protein is expressed in astrocytes as well as in neurons and localizes in the nucleus

Cytogenetic and Genome Research
L A KifayathullahAshraf U Mannan

Abstract

The MECP2 gene, located at Xq28, encodes methyl-CpG-binding protein 2 (MeCP2), which is frequently mutated (up to 90%) in Rett syndrome (RTT). RTT is a progressive neurodevelopmental disorder, which affects primarily girls during early childhood and it is one of the most common causes of mental retardation in females. R270X is one of the most frequent recurrent MECP2 mutations among RTT cohorts. The R270X mutation resides within the TRD-NLS (Transcription Repression Domain-Nuclear Localization Signal) region of MeCP2 and causes a more severe clinical phenotype with increased mortality as compared to other mutations. To evaluate the functional role of the R270X mutation, we generated a transgenic mouse model expressing MeCP2(270_EGFP) (human mutation equivalent) by BAC recombineering. The expression pattern of MeCP2(270_EGFP) was similar to that of endogenous MeCP2. Strikingly, MeCP2(270_EGFP) localizes in the nucleus, contrary to the conjecture that R270X could cause disruption of the NLS. In primary hippocampal cells, we show that MeCP2(270_EGFP) was expressed in astrocytes by colocalization with the astrocyte-specific marker glial fibrillary acidic protein. Our data showing expression of MeCP2(270_EGFP) in transgenic mice ast...Continue Reading

Citations

Jan 20, 2012·Cold Spring Harbor Perspectives in Biology·Huda Y Zoghbi, Mark F Bear
Jan 5, 2012·PloS One·D V Krishna PantakaniAshraf U Mannan
Mar 22, 2014·EMBO Molecular Medicine·Martesa TantraHannelore Ehrenreich
Dec 25, 2012·Trends in Neurosciences·Hiroaki WakeJunichi Nabekura
Sep 6, 2011·Redox Report : Communications in Free Radical Research·Silvia LeonciniJoussef Hayek
May 21, 2013·The American Journal of Pathology·Chiranjeevi BoddaAshraf U Mannan
Jul 13, 2018·Orphanet Journal of Rare Diseases·Stephen Shovlin, Daniela Tropea
Aug 8, 2019·International Journal of Molecular Sciences·Uri KahanovitchMichelle L Olsen
Oct 20, 2017·Frontiers in Molecular Neuroscience·Xu-Rui JinLan Xiao
Aug 8, 2015·The Journal of Biological Chemistry·Steven Andrew BakerHuda Yahya Zoghbi

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