ArticleThe Journal of clinical investigation2017
Elevating expression of MeCP2 T158M rescues DNA binding and Rett syndrome-like phenotypes.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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Who cites it
49 citing papers in PubMed, 69 citations in OpenAlex.
- Structures of MeCP2 bound to nucleosomes reveal distinct mechanisms of Rett syndrome mutations.bioRxiv : the preprint server for biology · 2026Article
- From Gene to Hope: Rett Syndrome and the Rise of Molecular Therapies.Molecular diagnosis & therapy · 2026Review
- MeCP2 gene dosage-dependent neurodevelopmentally restricted defects arise by aberrant activation of cell fate-determining bivalent genes.Nature communications · 2026Article
- Metformin Treatment Shows Beneficial Effects on RTT-Associated Phenotypical Deficits inPharmaceuticals (Basel, Switzerland) · 2026Article
- Early differential impact of MeCP2 mutations on functional networks in Rett syndrome patient-derived human cortical organoids.Nature communications · 2026Article
- Modulating alternative splicing ofScience translational medicine · 2026Article
- Article
- Recent advances in epigenetic therapeutics for Rett syndrome: from mechanisms to clinical trials.Frontiers in behavioral neuroscience · 2026Review
- Human MeCP2 binds to promoters and inhibits transcription in an unmethylated yeast genome.Genetics · 2025Article
- Mutation of MeCP2 at T158M Leads to Distinct Molecular and Phenotypic Abnormalities in Male and Female Mice.Cells · 2025Article
- Evidence of neuronal DNA damage in the brains of patients with Rett syndrome.Disease models & mechanisms · 2025Article
- Potentiation of group III metabotropic glutamate receptors positively affects neurophysiological features in a mouse model of Rett syndrome.The Journal of pharmacology and experimental therapeutics · 2025Article
- Independent genetic strategies define the scope and limits of CDKL5 deficiency disorder reversal.Cell reports. Medicine · 2025Article
- Site-blocking antisense oligonucleotides as a mechanism to fine-tune MeCP2 expression.RNA (New York, N.Y.) · 2024Article
- Testing the PEST hypothesis using relevant Rett mutations in MeCP2 E1 and E2 isoforms.Human molecular genetics · 2024Article
- Differential dynamics specify MeCP2 function at nucleosomes and methylated DNA.Nature structural & molecular biology · 2024Article
- RettDb: the Rett syndrome omics database to navigate the Rett syndrome genomic landscape.Database : the journal of biological databases and curation · 2024Article
- MeCP2 gene therapy ameliorates disease phenotype in mouse model for Pitt Hopkins syndrome.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- Article
- Overcoming genetic and cellular complexity to study the pathophysiology of X-linked intellectual disabilities.Journal of neurodevelopmental disorders · 2024Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
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 common RTT-associated missense mutation, MeCP2 T158M. We found that the T158M mutation impaired MECP2 binding to methylated DNA and destabilized MeCP2 protein in an age-dependent manner, leading to the development of RTT-like phenotypes in these mice. Genetic elevation of MeCP2 T158M expression ameliorated multiple RTT-like features, including motor dysfunction and breathing irregularities, in both male and female mice. These improvements were accompanied by increased binding of MeCP2 T158M to DNA. Further, we found that the ubiquitin/proteasome pathway was responsible for MeCP2 T158M degradation and that proteasome inhibition increased MeCP2 T158M levels. Together, these findings demonstrate that increasing MeCP2 T158M protein expression is sufficient to mitigate RTT-like phenotypes and support the targeting of MeCP2 T158M expression or stability as an alternative therapeutic approach.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.