ArticleNature genetics2013
A suppressor screen in Mecp2 mutant mice implicates cholesterol metabolism in Rett syndrome.
Article in Nature genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 133 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Biobanking of Rett Syndrome and Related Disorders Protocol
Rett Syndrome, MECP2 Duplication Disorder, and Rett- Related Disorders Natural History Protocol
Who cites it
133 citing papers in PubMed, 238 citations in OpenAlex.
- Effects of ω-3 PUFAs supplementation on myocardial function and oxidative stress markers in typical Rett syndrome.Mediators of inflammation · 2014Trial
- Sterol pathway disruption in pregnancy: a link to autism.Molecular psychiatry · 2026Article
- Metabolites with a message: impacts on epigenetics and implications for epimetabopathies.EMBO reports · 2026Review
- Mapping Trofinetide Polypharmacology in Rett Syndrome: A Multi-Stage Computational Analysis.Journal of computational chemistry · 2026Article
- Sterol biosynthesis, brain development, and disease.The Journal of clinical investigation · 2026Review
- Mechanistic Links Between DNA Methylation and Protein Translation and Their Impacts on Brain Development.Biology · 2026Review
- Dysregulated Cholesterol Clearance via CYP46A1 Contributes to Cerebellar Sterol Imbalance inInternational journal of molecular sciences · 2026Article
- Disrupted Vitamin D Signaling and Metabolism in Neurodevelopmental and Neurodegenerative Disorders.ASN neuro · 2026Review
- Serotonergic Signaling Rewired: A Lipid Raft-Controlled Model of Synaptic Transmission Grounded in the Fundamental Parameters of Biological Systems.Life (Basel, Switzerland) · 2026Article
- MECP2 Duplication Uncouples Mitochondrial and Purine Metabolism During neuronal maturation.bioRxiv : the preprint server for biology · 2025Article
- Rett syndrome: advances in Understanding MeCP2 function, potential gene therapies, and public health implications.Molecular biology reports · 2025Review
- NEAT1-mediated regulation of proteostasis and mRNA localization impacts autophagy dysregulation in Rett syndrome.Nucleic acids research · 2025Article
- Steatotic liver disease diagnosed in a 24-year-old woman with Rett syndrome: a case report.The Journal of international medical research · 2025Article
- Rett Syndrome: Thinking Beyond Brain Borders.Advances in experimental medicine and biology · 2025Review
- Proteomic analysis of serum from a MeCP2 patient reveals an arginine biosynthesis pathway affected by the p.Lys254* variant.Clinical case reports · 2024Article
- Rett syndrome.Nature reviews. Disease primers · 2024Review
- Rett Syndrome: The Emerging Landscape of Treatment Strategies.CNS drugs · 2024Review
- Unraveling autophagic imbalances and therapeutic insights in Mecp2-deficient models.EMBO molecular medicine · 2024Article
- Ex vivo disease modelling of Rett syndrome: the transcriptomic and metabolomic implications of direct neuronal conversion.Molecular biology reports · 2024Article
- Genetic Instability and Disease Progression of Indian Rett Syndrome Patients.Molecular neurobiology · 2024Article
73 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
- Commented on by
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Mutations in MECP2, encoding methyl CpG-binding protein 2, cause Rett syndrome, the most severe autism spectrum disorder. Re-expressing Mecp2 in symptomatic Mecp2-null mice markedly improves function and longevity, providing hope that therapeutic intervention is possible in humans. To identify pathways in disease pathology for therapeutic intervention, we carried out a dominant N-ethyl-N-nitrosourea (ENU) mutagenesis suppressor screen in Mecp2-null mice and isolated five suppressors that ameliorate the symptoms of Mecp2 loss. We show that a stop codon mutation in Sqle, encoding squalene epoxidase, a rate-limiting enzyme in cholesterol biosynthesis, underlies suppression in one line. Subsequently, we also show that lipid metabolism is perturbed in the brains and livers of Mecp2-null male mice. Consistently, statin drugs improve systemic perturbations of lipid metabolism, alleviate motor symptoms and confer increased longevity in Mecp2 mutant mice. Our genetic screen therefore points to cholesterol homeostasis as a potential target for the treatment of patients with Rett syndrome.
Indexed as
Identifiers
What OpenQuestion holds
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.