{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:57:26Z","timestamp":1790211446235,"version":"4.1.0"},"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2015,3,11]],"date-time":"2015-03-11T00:00:00Z","timestamp":1426032000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"DOI":"10.1371\/journal.pgen.1005043","type":"journal-article","created":{"date-parts":[[2015,3,11]],"date-time":"2015-03-11T17:56:55Z","timestamp":1426096615000},"page":"e1005043","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":53,"title":["Effects on Murine Behavior and Lifespan of Selectively Decreasing Expression of Mutant Huntingtin Allele by Supt4h Knockdown"],"prefix":"10.1371","volume":"11","author":[{"given":"Hui-Min","family":"Cheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijuang","family":"Chern","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I-Hui","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Rung","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sih-Huei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung J.","family":"Chun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Rigo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Frank","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chyuan-Sheng","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Ting","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley N.","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzu-Hao","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2015,3,11]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1146\/annurev.ge.29.120195.003415","article-title":"Trinucleotide repeat expansion and human disease","volume":"29","author":"CT Ashley Jr.","year":"1995","journal-title":"Annu Rev Genet"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1146\/annurev.neuro.29.051605.113042","article-title":"Trinucleotide repeat disorders","volume":"30","author":"HT Orr","year":"2007","journal-title":"Annu Rev Neurosci"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/nrm2854","article-title":"Repeat instability as the basis for human diseases and as a potential target for therapy","volume":"11","author":"A Lopez Castel","year":"2010","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref4","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a007476","article-title":"Huntington's Disease","volume":"3","author":"S Finkbeiner","year":"2011","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/0092-8674(93)90585-E","article-title":"A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group","volume":"72","year":"1993","journal-title":"Cell"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/S0896-6273(02)00872-3","article-title":"Polyglutamine pathogenesis: emergence of unifying mechanisms for Huntington's disease and related disorders","volume":"35","author":"CA Ross","year":"2002","journal-title":"Neuron"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1146\/annurev.neuro.23.1.217","article-title":"Glutamine repeats and neurodegeneration","volume":"23","author":"HY Zoghbi","year":"2000","journal-title":"Annu Rev Neurosci"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1038\/nrg1691","article-title":"Diseases of unstable repeat expansion: mechanisms and common principles","volume":"6","author":"JR Gatchel","year":"2005","journal-title":"Nat Rev Genet"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1093\/hmg\/9.6.909","article-title":"Fourteen and counting: unraveling trinucleotide repeat diseases","volume":"9","author":"CJ Cummings","year":"2000","journal-title":"Hum Mol Genet"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.bbagrm.2011.12.009","article-title":"Chromatin changes in the development and pathology of the Fragile X-associated disorders and Friedreich ataxia","volume":"1819","author":"D Kumari","year":"2012","journal-title":"Biochim Biophys Acta"},{"key":"ref11","article-title":"Myotonic dystrophies: An update on clinical aspects, genetic, pathology, and molecular pathomechanisms","author":"G Meola","year":"2014","journal-title":"Biochim Biophys Acta"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"226","DOI":"10.3389\/fgene.2014.00226","article-title":"Repeat-mediated genetic and epigenetic changes at the FMR1 locus in the Fragile X-related disorders","volume":"5","author":"K Usdin","year":"2014","journal-title":"Front Genet"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1016\/j.cell.2011.12.032","article-title":"Spt4 is selectively required for transcription of extended trinucleotide repeats","volume":"148","author":"CR Liu","year":"2012","journal-title":"Cell"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"e50717","DOI":"10.1371\/journal.pone.0050717","article-title":"Characterization of neurophysiological and behavioral changes, MRI brain volumetry and 1H MRS in zQ175 knock-in mouse model of Huntington's disease","volume":"7","author":"T Heikkinen","year":"2012","journal-title":"PLoS One"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"e49838","DOI":"10.1371\/journal.pone.0049838","article-title":"Comprehensive behavioral and molecular characterization of a new knock-in mouse model of Huntington's disease: zQ175","volume":"7","author":"LB Menalled","year":"2012","journal-title":"PLoS One"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/S0092-8674(00)81369-0","article-title":"Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice","volume":"87","author":"L Mangiarini","year":"1996","journal-title":"Cell"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1124\/jpet.113.212407","article-title":"Pharmacology of a central nervous system delivered 2'-O-methoxyethyl-modified survival of motor neuron splicing oligonucleotide in mice and nonhuman primates","volume":"350","author":"F Rigo","year":"2014","journal-title":"J Pharmacol Exp Ther"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.neuron.2012.05.009","article-title":"Sustained therapeutic reversal of Huntington's disease by transient repression of huntingtin synthesis","volume":"74","author":"HB Kordasiewicz","year":"2012","journal-title":"Neuron"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1038\/nbt.1539","article-title":"Allele-specific silencing of mutant huntingtin and ataxin-3 genes by targeting expanded CAG repeats in mRNAs","volume":"27","author":"J Hu","year":"2009","journal-title":"Nat Biotechnol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"5115","DOI":"10.1523\/JNEUROSCI.20-13-05115.2000","article-title":"Abnormal synaptic plasticity and impaired spatial cognition in mice transgenic for exon 1 of the human Huntington's disease mutation","volume":"20","author":"KP Murphy","year":"2000","journal-title":"J Neurosci"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/cne.10295","article-title":"Cellular localization and development of neuronal intranuclear inclusions in striatal and cortical neurons in R6\/2 transgenic mice","volume":"449","author":"CA Meade","year":"2002","journal-title":"J Comp Neurol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/ng1362","article-title":"Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease","volume":"36","author":"B Ravikumar","year":"2004","journal-title":"Nat Genet"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"11563","DOI":"10.1073\/pnas.0505321102","article-title":"Suppression of Huntington's disease pathology in Drosophila by human single-chain Fv antibodies","volume":"102","author":"WJ Wolfgang","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"2929","DOI":"10.1093\/hmg\/ddp230","article-title":"The A2A adenosine receptor rescues the urea cycle deficiency of Huntington's disease by enhancing the activity of the ubiquitin-proteasome system","volume":"18","author":"MC Chiang","year":"2009","journal-title":"Hum Mol Genet"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"6809","DOI":"10.1073\/pnas.120166397","article-title":"Severe deficiencies in dopamine signaling in presymptomatic Huntington's disease mice","volume":"97","author":"JA Bibb","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"18189","DOI":"10.1073\/pnas.0506375102","article-title":"FGF-2 promotes neurogenesis and neuroprotection and prolongs survival in a transgenic mouse model of Huntington's disease","volume":"102","author":"K Jin","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"3248","DOI":"10.1523\/JNEUROSCI.19-08-03248.1999","article-title":"Characterization of progressive motor deficits in mice transgenic for the human Huntington's disease mutation","volume":"19","author":"RJ Carter","year":"1999","journal-title":"J Neurosci"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"4328","DOI":"10.1093\/hmg\/ddu151","article-title":"Inhibition of soluble tumor necrosis factor is therapeutic in Huntington's disease","volume":"23","author":"HY Hsiao","year":"2014","journal-title":"Hum Mol Genet"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"26998","DOI":"10.1074\/jbc.273.41.26998","article-title":"Transcriptional properties of RNA polymerase II within triplet repeat-containing DNA from the human myotonic dystrophy and fragile X loci","volume":"273","author":"MA Parsons","year":"1998","journal-title":"J Biol Chem"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1126\/science.1059495","article-title":"Structural basis of transcription: an RNA polymerase II elongation complex at 3.3 A resolution","volume":"292","author":"AL Gnatt","year":"2001","journal-title":"Science"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"7444","DOI":"10.1093\/nar\/gkr429","article-title":"DNA slip-outs cause RNA polymerase II arrest in vitro: potential implications for genetic instability","volume":"39","author":"V Salinas-Rios","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1016\/j.str.2008.08.013","article-title":"Core structure of the yeast spt4-spt5 complex: a conserved module for regulation of transcription elongation","volume":"16","author":"M Guo","year":"2008","journal-title":"Structure"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1042\/BJ20091422","article-title":"Crystal structure of the human transcription elongation factor DSIF hSpt4 subunit in complex with the hSpt5 dimerization interface","volume":"425","author":"S Wenzel","year":"2010","journal-title":"Biochem J"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1073\/pnas.1013828108","article-title":"RNA polymerase and transcription elongation factor Spt4\/5 complex structure","volume":"108","author":"BJ Klein","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1038\/emboj.2011.64","article-title":"Architecture of the RNA polymerase-Spt4\/5 complex and basis of universal transcription processivity","volume":"30","author":"FW Martinez-Rucobo","year":"2011","journal-title":"EMBO J"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/BF00279450","article-title":"Molecular and genetic characterization of SPT4, a gene important for transcription initiation in Saccharomyces cerevisiae","volume":"237","author":"EA Malone","year":"1993","journal-title":"Mol Gen Genet"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1152\/physrev.00041.2009","article-title":"Molecular mechanisms and potential therapeutical targets in Huntington's disease","volume":"90","author":"C Zuccato","year":"2010","journal-title":"Physiol Rev"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1038\/81593","article-title":"Inactivation of Hdh in the brain and testis results in progressive neurodegeneration and sterility in mice","volume":"26","author":"I Dragatsis","year":"2000","journal-title":"Nat Genet"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.cell.2012.08.002","article-title":"Single-stranded RNAs use RNAi to potently and allele-selectively inhibit mutant huntingtin expression","volume":"150","author":"D Yu","year":"2012","journal-title":"Cell"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"5474","DOI":"10.1093\/nar\/gkm601","article-title":"Muscleblind-like 1 interacts with RNA hairpins in splicing target and pathogenic RNAs","volume":"35","author":"Y Yuan","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"8938","DOI":"10.1093\/nar\/gkr608","article-title":"CAG repeats mimic CUG repeats in the misregulation of alternative splicing","volume":"39","author":"A Mykowska","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1093\/nar\/gkr729","article-title":"Triplet repeat RNA structure and its role as pathogenic agent and therapeutic target","volume":"40","author":"WJ Krzyzosiak","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1089\/hum.2007.116","article-title":"Identification and allele-specific silencing of the mutant huntingtin allele in Huntington's disease patient-derived fibroblasts","volume":"19","author":"PH van Bilsen","year":"2008","journal-title":"Hum Gene Ther"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.cub.2009.03.030","article-title":"Five siRNAs targeting three SNPs may provide therapy for three-quarters of Huntington's disease patients","volume":"19","author":"EL Pfister","year":"2009","journal-title":"Curr Biol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1111\/j.1471-4159.2008.05734.x","article-title":"Allele-specific silencing of mutant Huntington's disease gene","volume":"108","author":"Y Zhang","year":"2009","journal-title":"J Neurochem"},{"key":"ref46","article-title":"In vivo evaluation of candidate allele-specific mutant huntingtin gene silencing antisense oligonucleotides","author":"AL Southwell","year":"2014","journal-title":"Mol Ther"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1038\/ncomms2514","article-title":"Translation of HTT mRNA with expanded CAG repeats is regulated by the MID1-PP2A protein complex","volume":"4","author":"S Krauss","year":"2013","journal-title":"Nat Commun"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"4382","DOI":"10.1111\/febs.12418","article-title":"Genetic manipulations of mutant huntingtin in mice: new insights into Huntington's disease pathogenesis","volume":"280","author":"CY Lee","year":"2013","journal-title":"FEBS J"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/S0165-6147(00)01884-8","article-title":"Mouse models of Huntington's disease","volume":"23","author":"LB Menalled","year":"2002","journal-title":"Trends Pharmacol Sci"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1007\/s13311-013-0194-5","article-title":"Antisense oligonucleotides: treating neurodegeneration at the level of RNA","volume":"10","author":"SL DeVos","year":"2013","journal-title":"Neurotherapeutics"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1101\/gad.14.4.452","article-title":"Yeast heterochromatin is a dynamic structure that requires silencers continuously","volume":"14","author":"TH Cheng","year":"2000","journal-title":"Genes Dev"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1093\/hmg\/8.7.1227","article-title":"Ultrastructural localization and progressive formation of neuropil aggregates in Huntington's disease transgenic mice","volume":"8","author":"H Li","year":"1999","journal-title":"Hum Mol Genet"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1093\/hmg\/ddt615","article-title":"FTY720 (fingolimod) is a neuroprotective and disease-modifying agent in cellular and mouse models of Huntington disease","volume":"23","author":"A Di Pardo","year":"2014","journal-title":"Hum Mol Genet"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"4043","DOI":"10.1093\/hmg\/ddq322","article-title":"Modulation of energy deficiency in Huntington's disease via activation of the peroxisome proliferator-activated receptor gamma","volume":"19","author":"MC Chiang","year":"2010","journal-title":"Hum Mol Genet"}],"container-title":["PLOS Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pgen.1005043","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,2]],"date-time":"2022-05-02T00:30:01Z","timestamp":1651451401000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1005043"}},"subtitle":[],"editor":[{"given":"Harry T.","family":"Orr","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,3,11]]},"references-count":54,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2015,3,11]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pgen.1005043","relation":{},"ISSN":["1553-7404"],"issn-type":[{"value":"1553-7404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3,11]]}}}