ArticleHuman mutation2014
The mismatch repair protein MSH2 is rate limiting for repeat expansion in a fragile X premutation mouse model.
Article in Human mutation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 82 citations in OpenAlex.
- Huntington disease: somatic expansion, pathobiology and therapeutics.Nature reviews. Neurology · 2026Review
- RNA/DNA-binding protein TDP43 regulates DNA mismatch repair genes with implications for genome stability.Nucleic acids research · 2025Article
- RNA/DNA Binding Protein TDP43 Regulates DNA Mismatch Repair Genes with Implications for Genome Stability.bioRxiv : the preprint server for biology · 2025Article
- Tissue-Specific Effects of the DNA Helicase FANCJ/BRIP1/BACH1 on Repeat Expansion in a Mouse Model of the Fragile X-Related Disorders.International journal of molecular sciences · 2025Article
- Repeat expansion in a fragile X model is independent of double strand break repair mediated by Pol θ, RAD52, RAD54 or RAD54B.Scientific reports · 2025Article
- Somatic Instability Leading to Mosaicism in Fragile X Syndrome and Associated Disorders: Complex Mechanisms, Diagnostics, and Clinical Relevance.International journal of molecular sciences · 2024Review
- Recurrent DNA nicks drive massive expansions of (GAA)Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Review
- Repeat expansion in a Fragile X model is independent of double strand break repair mediated by Pol θ, Rad52, Rad54l or Rad54b.bioRxiv : the preprint server for biology · 2024Article
- Somatic and intergenerational G4C2 hexanucleotide repeat instability in a human C9orf72 knock-in mouse model.Nucleic acids research · 2024Article
- Genetic modifiers of repeat expansion disorders.Emerging topics in life sciences · 2023Article
- Gene-Environment Interactions in Repeat Expansion Diseases: Mechanisms of Environmentally Induced Repeat Instability.Biomedicines · 2023Review
- Both cis and trans-acting genetic factors drive somatic instability in female carriers of the FMR1 premutation.Scientific reports · 2022Article
- Mechanisms of theInternational journal of molecular sciences · 2022Review
- A Double-Pronged Sword: XJB-5-131 Is a Suppressor of Somatic Instability and Toxicity in Huntington's Disease.Journal of Huntington's disease · 2022Review
- Non-canonical DNA/RNA structures associated with the pathogenesis of Fragile X-associated tremor/ataxia syndrome and Fragile X syndrome.Frontiers in genetics · 2022Review
- Review
- (Dys)function Follows Form: Nucleic Acid Structure, Repeat Expansion, and Disease Pathology inInternational journal of molecular sciences · 2021Review
- Review
- Somatic CAG expansion in Huntington's disease is dependent on the MLH3 endonuclease domain, which can be excluded via splice redirection.Nucleic acids research · 2021Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Fragile X-associated tremor and ataxia syndrome, Fragile X-associated primary ovarian insufficiency, and Fragile X syndrome are Repeat Expansion Diseases caused by expansion of a CGG•CCG-repeat microsatellite in the 5 UTR of the FMR1 gene. To help understand the expansion mechanism responsible for these disorders, we have crossed mice containing∼147 CGG•CCG repeats in the endogenous murine Fmr1 gene with mice containing a null mutation in the gene encoding the mismatch repair protein MSH2. MSH2 mutations are associated with elevated levels of generalized microsatellite instability. However, we show here for the first time that in the FX mouse model, all maternally and paternally transmitted expansions require Msh2. Even the loss of one Msh2 allele reduced the intergenerational expansion frequency significantly. Msh2 is also required for all somatic expansions and loss of even one functional Msh2 allele reduced the extent of somatic expansion in some organs. Tissues with lower levels of MSH2 were more sensitive to the loss of a single Msh2 allele. This suggests that MSH2 is rate limiting for expansion in this mouse model and that MSH2 levels may be a key factor that accounts for tissue-specific differences in expansion risk.
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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.