期刊
EUROPEAN JOURNAL OF HUMAN GENETICS
卷 20, 期 1, 页码 69-76出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ejhg.2011.145
关键词
Rett syndrome; MeCP2; alternative splicing; mouse model
资金
- FONDECYT [1061067, 1051079, 11070237]
- Chilean Government through Conicyt
Rett syndrome (RTT) is a disorder that affects patients' ability to communicate, move and behave. RTT patients are characterized by impaired language, stereotypic behaviors, frequent seizures, ataxia and sleep disturbances, with the onset of symptoms occurring after a period of seemingly normal development. RTT is caused by mutations in methyl-CpG binding protein 2 (MECP2), an X-chromosome gene encoding for MeCP2, a protein that regulates gene expression. MECP2 generates two alternative splice variants encoding two protein isoforms that differ only in the N-terminus. Although no functional differences have been identified for these splice variants, it has been suggested that the RTT phenotype may occur in the presence of a functional MeCP2-e2 protein. This suggests that the two isoforms might be functionally distinct. Supporting this notion, the two variants show regional and age-related differences in transcript abundance. Here, we show that transgenic expression of either the MeCP2-e1 or MeCP2-e2 splice variant results in prevention of development of RTT-like phenotypic manifestations in a mouse model lacking Mecp2. Our results indicate that the two MeCP2 splice variants can substitute for each other and fulfill the basic functions of MeCP2 in the mouse brain. European Journal of Human Genetics (2012) 20, 69-76; doi:10.1038/ejhg.2011.145; published online 10 August 2011
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