{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T18:20:01Z","timestamp":1764872401094},"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2013,9,23]],"date-time":"2013-09-23T00:00:00Z","timestamp":1379894400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0075108","type":"journal-article","created":{"date-parts":[[2013,9,24]],"date-time":"2013-09-24T01:27:18Z","timestamp":1379986038000},"page":"e75108","update-policy":"http:\/\/dx.doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":22,"title":["Mutant Huntingtin Gene-Dose Impacts on Aggregate Deposition, DARPP32 Expression and Neuroinflammation in HdhQ150 Mice"],"prefix":"10.1371","volume":"8","author":[{"given":"Douglas","family":"Young","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franziska","family":"Mayer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nella","family":"Vidotto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatjana","family":"Schweizer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramon","family":"Berth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorothee","family":"Abramowski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derya R.","family":"Shimshek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. Herman","family":"van der Putten","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Schmid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2013,9,23]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"2738","DOI":"10.1093\/hmg\/ddn175","article-title":"Accumulation of N-terminal mutant huntingtin in mouse and monkey models implicated as a pathogenic mechanism in Huntington's disease","volume":"17","author":"CE Wang","year":"2008","journal-title":"Hum Mol Genet"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"10855","DOI":"10.1074\/jbc.M804813200","article-title":"Mutant huntingtin N-terminal fragments of specific size mediate aggregation and toxicity in neuronal cells","volume":"284","author":"T Ratovitski","year":"2009","journal-title":"J Biol Chem"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"8808","DOI":"10.1074\/jbc.M109.075028","article-title":"Proteolysis of mutant huntingtin produces an exon 1 fragment that accumulates as an aggregated protein in neuronal nuclei in Huntington disease","volume":"285","author":"C Landles","year":"2010","journal-title":"J Biol Chem"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.1073\/pnas.1221891110","article-title":"Aberrant splicing of HTT generates the pathogenic exon 1 protein in Huntington disease","volume":"110","author":"K Sathasivam","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.expneurol.2011.12.013","article-title":"Protein aggregates in Huntington's disease","volume":"238","author":"M Arrasate","year":"2012","journal-title":"Exp Neurol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.1126\/science.277.5334.1990","article-title":"Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain","volume":"277","author":"M DiFiglia","year":"1997","journal-title":"Science"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"2522","DOI":"10.1523\/JNEUROSCI.19-07-02522.1999","article-title":"Nuclear and neuropil aggregates in Huntington's disease: relationship to neuropathology","volume":"19","author":"CA Gutekunst","year":"1999","journal-title":"J Neurosci"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1016\/S0140-6736(03)13304-1","article-title":"Huntingtin aggregation and toxicity in Huntington's disease","volume":"361","author":"G Bates","year":"2003","journal-title":"Lancet"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1038\/nature02998","article-title":"Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death","volume":"431","author":"M Arrasate","year":"2004","journal-title":"Nature"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1038\/nrm1742","article-title":"Opinion: What is the role of protein aggregation in neurodegeneration","volume":"6","author":"CA Ross","year":"2005","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"4246","DOI":"10.1073\/pnas.0511256103","article-title":"Pharmacological promotion of inclusion formation: a therapeutic approach for Huntington's and Parkinson's diseases","volume":"103","author":"RA Bodner","year":"2006","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.neuron.2010.12.035","article-title":"Huntington's disease: can mice lead the way to treatment?","volume":"69","author":"ZR Crook","year":"2011","journal-title":"Neuron"},{"key":"ref13","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":"ref14","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.brainresbull.2006.11.004","article-title":"The Hdh(Q150\/Q150) knock-in mouse model of HD and the R6\/2 exon 1 model develop comparable and widespread molecular phenotypes","volume":"72","author":"B Woodman","year":"2007","journal-title":"Brain Res Bull"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1002\/cne.10776","article-title":"Time course of early motor and neuropathological anomalies in a knock-in mouse model of Huntington's disease with 140 CAG repeats","volume":"465","author":"LB Menalled","year":"2003","journal-title":"J Comp Neurol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.chembiol.2011.12.020","article-title":"TR-FRET-based duplex immunoassay reveals an inverse correlation of soluble and aggregated mutant huntingtin in huntington's disease","volume":"19","author":"B Baldo","year":"2012","journal-title":"Chem Biol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"e44457","DOI":"10.1371\/journal.pone.0044457","article-title":"Mutant Huntingtin Form a Soluble Oligomer Pool That Declines with Aggregate Deposition upon Aging","volume":"7","author":"D Marcellin","year":"2012","journal-title":"PLoS One"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"8989","DOI":"10.1523\/JNEUROSCI.1830-07.2007","article-title":"Longitudinal evaluation of the Hdh(CAG)150 knock-in murine model of Huntington's disease","volume":"27","author":"MY Heng","year":"2007","journal-title":"J Neurosci"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"3702","DOI":"10.1093\/hmg\/ddq285","article-title":"Early autophagic response in a novel knock-in model of Huntington disease","volume":"19","author":"MY Heng","year":"2010","journal-title":"Hum Mol Genet"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"e8025","DOI":"10.1371\/journal.pone.0008025","article-title":"Formation of polyglutamine inclusions in a wide range of non-CNS tissues in the HdhQ150 knock-in mouse model of Huntington's disease","volume":"4","author":"H Moffitt","year":"2009","journal-title":"PLoS One"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1750-1326-7-12","article-title":"Improvement of neuropathology and transcriptional deficits in CAG 140 knock-in mice supports a beneficial effect of dietary curcumin in Huntington's disease","volume":"7","author":"MA Hickey","year":"2012","journal-title":"Mol Neurodegener"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.brainresbull.2011.03.014","article-title":"Light and electron microscopic characterization of the evolution of cellular pathology in the Hdh(CAG)150<\/sup> Huntington's disease knock-in mouse","volume":"88","author":"Z Bayram-Weston","year":"2011","journal-title":"Brain Res Bull"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1093\/brain\/awg077","article-title":"Homozygosity for CAG mutation in Huntington disease is associated with a more severe clinical course","volume":"126","author":"F Squitieri","year":"2003","journal-title":"Brain"},{"key":"ref24","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-PP2Aprotein complex","volume":"4","author":"S Krauss","year":"2013","journal-title":"Nat Commun"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/ng0893-387","article-title":"Trinucleotide repeat length instability and age of onset in Huntington's disease","volume":"4","author":"M Duyao","year":"1993","journal-title":"Nat Genet"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1093\/hmg\/2.10.1547","article-title":"Correlation between the onset age of Huntington's disease and length of the trinucleotide repeat in IT-15","volume":"2","author":"OC Stine","year":"1993","journal-title":"Hum Mol Genet"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"3065","DOI":"10.1093\/hmg\/ddi340","article-title":"Contribution of nuclear and extranuclear polyQ to neurological phenotypes in mouse models of Huntington's disease","volume":"14","author":"CL Benn","year":"2005","journal-title":"Hum Mol Genet"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1016\/j.cell.2006.04.026","article-title":"Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin","volume":"16","author":"RK Graham","year":"2006","journal-title":"Cell"},{"key":"ref29","first-page":"397","article-title":"Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtin","volume":"8","author":"G Schilling","year":"1999","journal-title":"Hum Mol Genet"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"17204","DOI":"10.1073\/pnas.0708285104","article-title":"Therapeutic silencing of mutant huntingtin with siRNA attenuates striatal and cortical neuropathology and behavioral deficits","volume":"104","author":"M DiFiglia","year":"2007","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"5820","DOI":"10.1073\/pnas.0501507102","article-title":"RNA interference improves motor and neuropathological abnormalities in a Huntington's disease mouse model","volume":"102","author":"SQ Harper","year":"2005","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.neures.2005.06.021","article-title":"Clinico-pathological rescue of a model mouse of Huntington's disease by siRNA","volume":"53","author":"YL Wang","year":"2005","journal-title":"Neurosci Res"},{"key":"ref33","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":"ref34","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0361-9230(01)00599-8","article-title":"New anti-huntingtin monoclonal antibodies: implications for huntingtin conformation and its binding proteins","volume":"56","author":"J Ko","year":"2001","journal-title":"Brain Res Bull"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"21647","DOI":"10.1074\/jbc.M109.016923","article-title":"Monoclonal antibodies recognize distinct conformational epitopes formed by polyglutamine in a mutant huntingtin fragment","volume":"284","author":"J Legleiter","year":"2009","journal-title":"J Biol Chem"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1750-1326-4-11","article-title":"Inducible mutant huntingtin expression in HN10 cells reproduces Huntington'sdisease-like neuronal dysfunction","volume":"4","author":"A Weiss","year":"2009","journal-title":"Mol Neurodegener"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1146\/annurev.pharmtox.44.101802.121415","article-title":"DARPP-32: an integrator of neurotransmission","volume":"44","author":"P Svenningsson","year":"2004","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"9723","DOI":"10.1523\/JNEUROSCI.3044-08.2008","article-title":"Dysregulation of gene expression in primary neuron models of Huntington's disease shows that polyglutamine-related effects on the striatal transcriptome may not be dependent on brain circuitry","volume":"28","author":"H Runne","year":"2008","journal-title":"J Neurosci"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1093\/hmg\/ddq548","article-title":"In vivo cell-autonomous transcriptional abnormalities revealed in mice expressing mutant huntingtin in striatal but not cortical neurons","volume":"20","author":"EA Thomas","year":"2011","journal-title":"Hum Mol Genet"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.pneurobio.2007.03.004","article-title":"Transcriptional signatures in Huntington's disease","volume":"83","author":"JH Cha","year":"2007","journal-title":"Prog Neurobiol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"3351","DOI":"10.1093\/hmg\/11.26.3351","article-title":"Progressive retinal degeneration and dysfunction in R6 Huntington's disease mice","volume":"11","author":"D Helmlinger","year":"2002","journal-title":"Hum Mol Genet"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1002\/cne.20327","article-title":"Fine-structural analysis and connexin expression in the retina of a transgenic model of Huntington's disease","volume":"479","author":"E Petrasch-Parwez","year":"2004","journal-title":"J Comp Neurol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/j.nbd.2011.12.004","article-title":"Retinal dysfunction, photoreceptor protein dysregulation and neuronal remodelling in the R6\/1 mouse model of Huntington's disease","volume":"45","author":"AH Batcha","year":"2012","journal-title":"Neurobiol Dis"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1007\/s00702-010-0430-7","article-title":"Neuroinflammation in Huntington's disease","volume":"117","author":"T M\u00f6llern","year":"2010","journal-title":"J Neural Transm"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1111\/j.1471-4159.2007.05032.x","article-title":"Sensitive biochemical aggregate detection reveals aggregation onset before symptom development in cellular and murine models of Huntington's disease","volume":"104","author":"A Weiss","year":"2008","journal-title":"J Neurochem"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/B978-0-444-52014-2.00004-5","article-title":"Huntington\u2019s diesease \u2013Neuropathology","volume":"100","author":"JP Vonsattel","year":"2011","journal-title":"Handb Clin Neurol"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1212\/WNL.0b013e31826e9a5d","article-title":"Assessment of cortical and striatal involvement in 523 Huntington disease brains","volume":"79","author":"TC Hadzi","year":"2012","journal-title":"Neurology"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1093\/hmg\/ddl125","article-title":"Genetic background modifies nuclear mutant huntingtin accumulation and HD CAG repeat instability in Huntington's disease knock-in mice","volume":"15","author":"A Lloret","year":"2006","journal-title":"Hum Mol Genet"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0079-6123(07)63001-5","article-title":"The dentate gyrus: fundamental neuroanatomical organization (dentate gyrus for dummies)","volume":"163","author":"DG Amaral","year":"2007","journal-title":"Prog Brain Res"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1146\/annurev.pharmtox.44.101802.121415","article-title":"DARPP\u201332: an integrator of neurotransmission","volume":"44","author":"P Svenningsson","year":"2004","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"ref51","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 USA"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"3751","DOI":"10.1097\/00001756-200011270-00032","article-title":"N-Acetylaspartate and DARPP-32 levels decrease in the corpus striatum of Huntington's disease mice","volume":"11","author":"A van Dellen","year":"2000","journal-title":"Neuroreport"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"15491","DOI":"10.1073\/pnas.1212899109","article-title":"Conditional ablation of brain-derived neurotrophic factor-TrkB signaling impairs striatal neuron development","volume":"109","author":"Y Li","year":"2012","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1038\/nrneurol.2009.54","article-title":"Brain-derived neurotrophic factor in neurodegenerative diseases","volume":"5","author":"C Zuccato","year":"2009","journal-title":"Nat Rev Neurol"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1007\/s00401-005-1092-7","article-title":"Is the retina affected in Huntington disease?","volume":"110","author":"E Petrasch-Parwez","year":"2005","journal-title":"Acta Neuropathol"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1212\/01.wnl.0000222734.56412.17","article-title":"Microglial activation correlates with severity in Huntington disease: a clinical and PET study","volume":"66","author":"N Pavese","year":"2006","journal-title":"Neurology"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1002\/hbm.21008","article-title":"Microglial activation in regions related to cognitive function predicts disease onset in Huntington's disease: a multimodal imaging study","volume":"32","author":"M Politis","year":"2011","journal-title":"Hum Brain Mapp"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1093\/brain\/awm044","article-title":"Microglial activation in presymptomatic Huntington's disease gene carriers","volume":"130","author":"YF Tai","year":"2007","journal-title":"Brain"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.brainresbull.2006.10.029","article-title":"Imaging microglial activation in Huntington's disease","volume":"30","author":"YF Tai","year":"2007","journal-title":"Brain Res Bull"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1002\/glia.20526","article-title":"Ferritin accumulation in dystrophic microglia is an early event in the development of Huntington's disease","volume":"55","author":"DA Simmons","year":"2007","journal-title":"Glia"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0075108","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,18]],"date-time":"2024-05-18T03:29:31Z","timestamp":1716002971000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0075108"}},"subtitle":[],"editor":[{"given":"J\u00f6rg","family":"Tatzelt","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2013,9,23]]},"references-count":60,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2013,9,23]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0075108","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,9,23]]}}}