ArticleHuman molecular genetics2014
Mice with an isoform-ablating Mecp2 exon 1 mutation recapitulate the neurologic deficits of Rett syndrome.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 82 citations in OpenAlex.
- Disruption of major Ptchd1 isoforms causes autistic traits in social behavior and communication.Molecular psychiatry · 2026Article
- Single-dose administration of therapeutic divalent siRNA targeting MECP2 prevents lethality in an MECP2 duplication mouse model.Nature communications · 2026Article
- Female cortical cellular mosaicism underlies shared MeCP2 and PCB impacted gene pathways.iScience · 2026Article
- Modulating alternative splicing ofScience translational medicine · 2026Article
- MeCP2 functions as a DNA methylation reader in immune homeostasis and cancer.Frontiers in epigenetics and epigenomics · 2026Review
- Human MeCP2 binds to promoters and inhibits transcription in an unmethylated yeast genome.Genetics · 2025Article
- Exploring the complexity of MECP2 function in Rett syndrome.Nature reviews. Neuroscience · 2025Review
- Up-Frameshift Factors from Phytopathogenic Fungi Play a Crucial Role in Nonsense-Mediated mRNA Decay.Journal of fungi (Basel, Switzerland) · 2025Article
- Neuronal Plasticity-Dependent Paradigm and Young Plasma Treatment Prevent Synaptic and Motor Deficit in a Rett Syndrome Mouse Model.Biomolecules · 2025Article
- SRSF9-Mediated Exon Recognition Promotes Exon 2 Inclusion inInternational journal of molecular sciences · 2025Article
- NEXMIF overexpression is associated with autism-like behaviors and alterations in dendritic arborization and spine formation in mice.Frontiers in neuroscience · 2025Article
- Sex-specific single cell-level transcriptomic signatures of Rett syndrome disease progression.Communications biology · 2024Article
- Sex-specific single cell-level transcriptomic signatures of Rett syndrome disease progression.bioRxiv : the preprint server for biology · 2024Article
- Epigenetics in rare neurological diseases.Frontiers in cell and developmental biology · 2024Review
- Post-transcriptional regulation of the transcriptional apparatus in neuronal development.Frontiers in molecular neuroscience · 2024Review
- The Epigenetic Reader Methyl-CpG-Binding Protein 2 (MeCP2) Is an Emerging Oncogene in Cancer Biology.Cancers · 2023Review
- MeCP2 Is an Epigenetic Factor That Links DNA Methylation with Brain Metabolism.International journal of molecular sciences · 2023Review
- Advanced genetic therapies for the treatment of Rett syndrome: state of the art and future perspectives.Frontiers in neuroscience · 2023Review
- The Chromatin Structure at theInternational journal of molecular sciences · 2022Article
- Differential Sensitivity of the Protein Translation Initiation Machinery and mTOR Signaling toCells · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
Mutations in MECP2 cause the neurodevelopmental disorder Rett syndrome (RTT OMIM 312750). Alternative inclusion of MECP2/Mecp2 exon 1 with exons 3 and 4 encodes MeCP2-e1 or MeCP2-e2 protein isoforms with unique amino termini. While most MECP2 mutations are located in exons 3 and 4 thus affecting both isoforms, MECP2 exon 1 mutations but not exon 2 mutations have been identified in RTT patients, suggesting that MeCP2-e1 deficiency is sufficient to cause RTT. As expected, genetic deletion of Mecp2 exons 3 and/or 4 recapitulates RTT-like neurologic defects in mice. However, Mecp2 exon 2 knockout mice have normal neurologic function. Here, a naturally occurring MECP2 exon 1 mutation is recapitulated in a mouse model by genetic engineering. A point mutation in the translational start codon of Mecp2 exon 1, transmitted through the germline, ablates MeCP2-e1 translation while preserving MeCP2-e2 production in mouse brain. The resulting MeCP2-e1 deficient mice developed forelimb stereotypy, hindlimb clasping, excessive grooming and hypo-activity prior to death between 7 and 31 weeks. MeCP2-e1 deficient mice also exhibited abnormal anxiety, sociability and ambulation. Despite MeCP2-e1 and MeCP2-e2 sharing, 96% amino acid identity, differences were identified. A fraction of phosphorylated MeCP2-e1 differed from the bulk of MeCP2 in subnuclear localization and co-factor interaction. Furthermore, MeCP2-e1 exhibited enhanced stability compared with MeCP2-e2 in neurons. Therefore, MeCP2-e1 deficient mice implicate MeCP2-e1 as the sole contributor to RTT with non-redundant functions.
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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.