ArticlePLoS genetics2015
Effects on murine behavior and lifespan of selectively decreasing expression of mutant huntingtin allele by supt4h knockdown.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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
33 citing papers in PubMed, 52 citations in OpenAlex.
- A fly model of SCA36 reveals combinatorial neurotoxicity of hexanucleotide and dipeptide repeats.PLoS genetics · 2025Article
- Lowering mutant huntingtin by small molecules relieves Huntington's disease symptoms and progression.EMBO molecular medicine · 2024Article
- The transcription elongation factors Spt4 and Spt5 control neural progenitor proliferation and are implicated in neuronal remodeling duringFrontiers in cell and developmental biology · 2024Article
- Binding of small molecule inhibitors to RNA polymerase-Spt5 complex impacts RNA and DNA stability.Journal of computer-aided molecular design · 2023Article
- Transcriptional elongation control in developmental gene expression, aging, and disease.Molecular cell · 2023Review
- Rare variant modifier analysis identifies variants in SEC24D associated with orofacial cleft subtypes.Human genetics · 2023Article
- Transcription elongation factors OsSPT4 and OsSPT5 are essential for rice growth and development and act with APO2.Plant cell reports · 2023Article
- Rare genetic variants inmedRxiv : the preprint server for health sciences · 2023Article
- DSIF modulates RNA polymerase II occupancy according to template G + C content.NAR genomics and bioinformatics · 2022Article
- Chemical interference with DSIF complex formation lowers synthesis of mutant huntingtin gene products and curtails mutant phenotypes.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Partners in crime: Proteins implicated in RNA repeat expansion diseases.Wiley interdisciplinary reviews. RNA · 2022Review
- Molecular Therapies for Myotonic Dystrophy Type 1: From Small Drugs to Gene Editing.International journal of molecular sciences · 2022Review
- The transient Spt4-Spt5 complex as an upstream regulator of non-coding RNAs during development.Nucleic acids research · 2022Article
- SUPT4H1-edited stem cell therapy rescues neuronal dysfunction in a mouse model for Huntington's disease.NPJ Regenerative medicine · 2022Article
- Current and Possible Future Therapeutic Options for Huntington's Disease.Journal of central nervous system disease · 2022Review
- Toxicity of pathogenic ataxin-2 in Drosophila shows dependence on a pure CAG repeat sequence.Human molecular genetics · 2021Article
- Opposite roles of transcription elongation factors Spt4/5 and Elf1 in RNA polymerase II transcription through B-form versus non-B DNA structures.Nucleic acids research · 2021Article
- Huntington's Disease: New Frontiers in Therapeutics.Current neurology and neuroscience reports · 2021Review
- Huntington disease: new insights into molecular pathogenesis and therapeutic opportunities.Nature reviews. Neurology · 2020Review
- New Roles for Canonical Transcription Factors in Repeat Expansion Diseases.Trends in genetics : TIG · 2020Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
Production of protein containing lengthy stretches of polyglutamine encoded by multiple repeats of the trinucleotide CAG is a hallmark of Huntington's disease (HD) and of a variety of other inherited degenerative neurological and neuromuscular disorders. Earlier work has shown that interference with production of the transcription elongation protein SUPT4H results in decreased cellular capacity to transcribe mutant huntingtin gene (Htt) alleles containing long CAG expansions, but has little effect on expression of genes containing short CAG stretches. zQ175 and R6/2 are genetically engineered mouse strains whose genomes contain human HTT alleles that include greatly expanded CAG repeats and which are used as animal models for HD. Here we show that reduction of SUPT4H expression in brains of zQ175 mice by intracerebroventricular bolus injection of antisense 2'-O-methoxyethyl oligonucleotides (ASOs) directed against Supt4h, or in R6/2 mice by deletion of one copy of the Supt4h gene, results in a decrease in mRNA and protein encoded specifically by mutant Htt alleles. We further show that reduction of SUPT4H in mouse brains is associated with decreased HTT protein aggregation, and in R6/2 mice, also with prolonged lifespan and delay of the motor impairment that normally develops in these animals. Our findings support the view that targeting of SUPT4H function may be useful as a therapeutic countermeasure against HD.
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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.