Radically truncated MeCP2 rescues Rett syndrome-like neurological defects
نویسندگان
چکیده
منابع مشابه
Elevating expression of MeCP2 T158M rescues DNA binding and Rett syndrome-like phenotypes.
Mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2) cause Rett syndrome (RTT), a neurological disorder affecting cognitive development, respiration, and motor function. Genetic restoration of MeCP2 expression reverses RTT-like phenotypes in mice, highlighting the need to search for therapeutic approaches. Here, we have developed knockin mice recapitulating the most comm...
متن کاملMeCP2 SUMOylation rescues Mecp2-mutant-induced behavioural deficits in a mouse model of Rett syndrome
The methyl-CpG-binding protein 2 (MeCP2) gene, MECP2, is an X-linked gene encoding the MeCP2 protein, and mutations of MECP2 cause Rett syndrome (RTT). However, the molecular mechanism of MECP2-mutation-caused RTT is less known. Here we find that MeCP2 could be SUMO-modified by the E3 ligase PIAS1 at Lys-412. MeCP2 phosphorylation (at Ser-421 and Thr-308) facilitates MeCP2 SUMOylation, and MeCP...
متن کاملRett syndrome and the MECP2 gene.
First described by Andreas Rett in 1966, Rett syndrome is a severe neurodevelopmental disorder which almost exclusively aVects females. A genetic aetiology was suggested by MZ twin concordance and a case of vertical transmission of the disorder. Although the prevalence is between 1 in 10 000 and 1 in 15 000 female births, >95% of cases arise de novo so the disorder has been considered to be an ...
متن کاملSystemic delivery of MeCP2 rescues behavioral and cellular deficits in female mouse models of Rett syndrome.
De novo mutations in the X-linked gene encoding the transcription factor methyl-CpG binding protein 2 (MECP2) are the most frequent cause of the neurological disorder Rett syndrome (RTT). Hemizygous males usually die of neonatal encephalopathy. Heterozygous females survive into adulthood but exhibit severe symptoms including microcephaly, loss of purposeful hand motions and speech, and motor ab...
متن کاملExpression of MeCP2 in postmitotic neurons rescues Rett syndrome in mice.
Mutations in MECP2 are the cause of Rett syndrome (RTT) in humans, a neurodevelopmental disorder that affects mainly girls. MeCP2 is a protein that binds CpG dinucleotides and is thought to act as a global transcriptional repressor. It is highly expressed in neurons, but not in glia, of the postnatal brain. The timing of MeCP2 activation correlates with the maturation of the central nervous sys...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Nature
سال: 2017
ISSN: 0028-0836,1476-4687
DOI: 10.1038/nature24058