ArticlePloS one2011
Long tract of untranslated CAG repeats is deleterious in transgenic mice.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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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.
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Who cites it
43 citing papers in PubMed, 65 citations in OpenAlex.
- Insights into RNA-mediated pathology in new mouse models of Huntington's disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- The length of uninterrupted CAG repeats in stem regions of repeat disease associated hairpins determines the amount of short CAG oligonucleotides that are toxic to cells through RNA interference.Cell death & disease · 2022Article
- Review
- Current Status of Gene Therapy Research in Polyglutamine Spinocerebellar Ataxias.International journal of molecular sciences · 2021Review
- Huntington disease: new insights into molecular pathogenesis and therapeutic opportunities.Nature reviews. Neurology · 2020Review
- Interferon mediated neuroinflammation in polyglutamine disease is not caused by RNA toxicity.Cell death & disease · 2020Article
- PolyQ-independent toxicity associated with novel translational products from CAG repeat expansions.PloS one · 2020Article
- Trinucleotide Repeat Expansion Diseases, RNAi, and Cancer.Trends in cancer · 2018Review
- Design of Bivalent Nucleic Acid Ligands for Recognition of RNA-Repeated Expansion Associated with Huntington's Disease.Biochemistry · 2018Article
- Small interfering RNAs based on huntingtin trinucleotide repeats are highly toxic to cancer cells.EMBO reports · 2018Article
- Protein sequestration as a normal function of long noncoding RNAs and a pathogenic mechanism of RNAs containing nucleotide repeat expansions.Human genetics · 2017Review
- Trojan triplets: RNA-based pathomechanisms for muscle dysfunction in Huntington's disease.The Journal of general physiology · 2017Article
- Review
- RNA toxicity induced by expanded CAG repeats in Huntington's disease.Brain pathology (Zurich, Switzerland) · 2016Review
- The first crystal structures of RNA-PNA duplexes and a PNA-PNA duplex containing mismatches--toward anti-sense therapy against TREDs.Nucleic acids research · 2016Article
- In Vitro Expansion of CAG, CAA, and Mixed CAG/CAA Repeats.International journal of molecular sciences · 2015Article
- The role of the immune system in triplet repeat expansion diseases.Mediators of inflammation · 2015Review
- RAN translation and frameshifting as translational challenges at simple repeats of human neurodegenerative disorders.Nucleic acids research · 2014Review
- Oligonucleotide-based strategies to combat polyglutamine diseases.Nucleic acids research · 2014Review
- Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The most frequent trinucleotide repeat found in human disorders is the CAG sequence. Expansion of CAG repeats is mostly found in coding regions and is thought to cause diseases through a protein mechanism. Recently, expanded CAG repeats were shown to induce toxicity at the RNA level in Drosophila and C. elegans. These findings raise the possibility that CAG repeats may trigger RNA-mediated pathogenesis in mammals. Here, we demonstrate that transgenic mice expressing EGFP transcripts with long CAG repeats in the 3' untranslated region develop pathogenic features. Expression of the transgene was directed to the muscle in order to compare the resulting phenotype to that caused by the CUG expansion, as occurs in myotonic dystrophy. Transgenic mice expressing 200, but not those expressing 0 or 23 CAG repeats, showed alterations in muscle morphology, histochemistry and electrophysiology, as well as abnormal behavioral phenotypes. Expression of the expanded CAG repeats in testes resulted in reduced fertility due to defective sperm motility. The production of EGFP protein was significantly reduced by the 200 CAG repeats, and no polyglutamine-containing product was detected, which argues against a protein mechanism. Moreover, nuclear RNA foci were detected for the long CAG repeats. These data support the notion that expanded CAG repeat RNA can cause deleterious effects in mammals. They also suggest the possible involvement of an RNA mechanism in human diseases with long CAG repeats.
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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.