ArticleEMBO molecular medicine2014
Mild expression differences of MECP2 influencing aggressive social behavior.
Article in EMBO molecular medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Forebrain-specific loss of erythropoietin provokes compensatory upregulation of different EPO receptors.Molecular psychiatry · 2026Article
- Stress enhances aggression in male rats with genetic stress hyper-reactivity.Genes, brain, and behavior · 2024Article
- A small-molecule TrkB ligand improves dendritic spine phenotypes and atypical behaviors in female Rett syndrome mice.Disease models & mechanisms · 2024Article
- Prognostic Impact of Genetic Variants of MECP2 and TIRAP on Clinical Outcomes of Systemic Lupus Erythematosus with and without Nephritis.Biomolecules · 2021Article
- Regulation, diversity and function of MECP2 exon and 3'UTR isoforms.Human molecular genetics · 2020Review
- A new sex-specific underlying mechanism for female schizophrenia: accelerated skewed X chromosome inactivation.Biology of sex differences · 2020Article
- The BEACH Protein LRBA Promotes the Localization of the Heterotrimeric G-protein GScientific reports · 2017Article
- Methyl-CpG binding domain proteins inhibit interspecies courtship and promote aggression in Drosophila.Scientific reports · 2017Article
- Long-term consumption of sugar-sweetened beverage during the growth period promotes social aggression in adult mice with proinflammatory responses in the brain.Scientific reports · 2017Article
- Article
- The Neurobiological Basis for Social Affiliation in Autism Spectrum Disorder and Schizophrenia.Current behavioral neuroscience reports · 2016Article
- The SocioBox: A Novel Paradigm to Assess Complex Social Recognition in Male Mice.Frontiers in behavioral neuroscience · 2016Article
- Applying the ethoexperimental approach to neurodevelopmental syndrome research reveals exaggerated defensive behavior in Mecp2 mutant mice.Physiology & behavior · 2015Article
- Integrated analysis of whole-exome sequencing and transcriptome profiling in males with autism spectrum disorders.Molecular autism · 2015Article
- Regulatory functions and pathological relevance of the MECP2 3'UTR in the central nervous system.Cell regeneration (London, England) · 2015Article
- Atypical social behaviors in mouse models for Rett syndrome.Frontiers in neurologyReview
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The X-chromosomal MECP2/Mecp2 gene encodes methyl-CpG-binding protein 2, a transcriptional activator and repressor regulating many other genes. We discovered in male FVB/N mice that mild (~50%) transgenic overexpression of Mecp2 enhances aggression. Surprisingly, when the same transgene was expressed in C57BL/6N mice, transgenics showed reduced aggression and social interaction. This suggests that Mecp2 modulates aggressive social behavior. To test this hypothesis in humans, we performed a phenotype-based genetic association study (PGAS) in >1000 schizophrenic individuals. We found MECP2 SNPs rs2239464 (G/A) and rs2734647 (C/T; 3'UTR) associated with aggression, with the G and C carriers, respectively, being more aggressive. This finding was replicated in an independent schizophrenia cohort. Allele-specific MECP2 mRNA expression differs in peripheral blood mononuclear cells by ~50% (rs2734647: C > T). Notably, the brain-expressed, species-conserved miR-511 binds to MECP2 3'UTR only in T carriers, thereby suppressing gene expression. To conclude, subtle MECP2/Mecp2 expression alterations impact aggression. While the mouse data provides evidence of an interaction between genetic background and mild Mecp2 overexpression, the human data convey means by which genetic variation affects MECP2 expression and behavior.
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