{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T03:40:26Z","timestamp":1784950826192,"version":"3.55.0"},"reference-count":116,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2013,11,22]],"date-time":"2013-11-22T00:00:00Z","timestamp":1385078400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0080923","type":"journal-article","created":{"date-parts":[[2013,11,22]],"date-time":"2013-11-22T23:01:40Z","timestamp":1385161300000},"page":"e80923","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":36,"title":["A Broad Phenotypic Screen Identifies Novel Phenotypes Driven by a Single Mutant Allele in Huntington\u2019s Disease CAG Knock-In Mice"],"prefix":"10.1371","volume":"8","author":[{"given":"Sabine M.","family":"H\u00f6lter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Stromberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Kovalenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lillian","family":"Garrett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Glasl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith","family":"Lopez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolene","family":"Guide","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"G\u00f6tz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Hans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lore","family":"Becker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Rathkolb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Rozman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Schrewed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Klingenspor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Klopstock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Schulz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eckhard","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Wursta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammy","family":"Gillis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Wakimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Seidman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcy E.","family":"MacDonald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Cotman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Gailus-Durner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Fuchs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin Hrab\u011b","family":"de Angelis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Min","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa C.","family":"Wheeler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2013,11,22]]},"reference":[{"key":"ref1","first-page":"957","article-title":"Huntington's disease: a clinical, genetic and molecular model for polyglutamine repeat disorders","volume":"354","author":"PS Harper","year":"1999","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/S1474-4422(09)70178-4","article-title":"Beyond the brain: widespread pathology in Huntington's disease","volume":"8","author":"JM van der Burg","year":"2009","journal-title":"Lancet Neurol"},{"key":"ref3","article-title":"Huntington's disease collaborative research group","year":"1993"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1212\/WNL.0b013e318249f683","article-title":"CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion","volume":"78","author":"JM Lee","year":"2012","journal-title":"Neurology"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1093\/hmg\/ddp524","article-title":"Huntingtin facilitates polycomb repressive complex 2","volume":"19","author":"IS Seong","year":"2010","journal-title":"Hum Mol Genet"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"2846","DOI":"10.1093\/hmg\/ddr195","article-title":"HD CAG-correlated gene expression changes support a simple dominant gain of function","volume":"20","author":"JC Jacobsen","year":"2011","journal-title":"Hum Mol Genet"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nbd.2008.06.005","article-title":"Rodent genetic models of Huntington disease","volume":"32","author":"MY Heng","year":"2008","journal-title":"Neurobiol Dis"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/ng1297-404","article-title":"Huntingtin is required for neurogenesis and is not impaired by the Huntington's disease CAG expansion","volume":"17","author":"JK White","year":"1997","journal-title":"Nat Genet"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1093\/hmg\/8.1.115","article-title":"Length-dependent gametic CAG repeat instability in the Huntington's disease knock-in mouse","volume":"8","author":"VC Wheeler","year":"1999","journal-title":"Hum Mol Genet"},{"key":"ref10","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":"ref11","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1093\/hmg\/9.4.503","article-title":"Long glutamine tracts cause nuclear localization of a novel form of huntingtin in medium spiny striatal neurons in HdhQ92 and HdhQ111 knock-in mice","volume":"9","author":"VC Wheeler","year":"2000","journal-title":"Hum Mol Genet"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1093\/hmg\/11.6.633","article-title":"Early phenotypes that presage late-onset neurodegenerative disease allow testing of modifiers in Hdh CAG knock-in mice","volume":"11","author":"VC Wheeler","year":"2002","journal-title":"Hum Mol Genet"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1093\/hmg\/11.19.2233","article-title":"Identification of a presymptomatic molecular phenotype in Hdh CAG knock-in mice","volume":"11","author":"E Fossale","year":"2002","journal-title":"Hum Mol Genet"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"18167","DOI":"10.1074\/jbc.M109.018325","article-title":"Rrs1 is involved in endoplasmic reticulum stress response in Huntington disease","volume":"284","author":"A Carnemolla","year":"2009","journal-title":"J Biol Chem"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1093\/hmg\/ddg046","article-title":"Specific progressive cAMP reduction implicates energy deficit in presymptomatic Huntington's disease knock-in mice","volume":"12","author":"S Gines","year":"2003","journal-title":"Hum Mol Genet"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1111\/j.1460-9568.2006.04590.x","article-title":"Reduced expression of the TrkB receptor in Huntington's disease mouse models and in human brain","volume":"23","author":"S Gin\u00e9s","year":"2006","journal-title":"Eur J Neurosci"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1523\/JNEUROSCI.4974-09.2010","article-title":"Metabotropic glutamate receptor-mediated cell signaling pathways are altered in a mouse model of Huntington's disease","volume":"30","author":"FM Ribeiro","year":"2010","journal-title":"J Neurosci"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"4424","DOI":"10.1523\/JNEUROSCI.5113-06.2007","article-title":"Brain-derived neurotrophic factor restores synaptic plasticity in a knock-in mouse model of Huntington's disease","volume":"27","author":"G Lynch","year":"2007","journal-title":"J Neurosci"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.nbd.2009.05.007","article-title":"Systematic behavioral evaluation of Huntington's disease transgenic and knock-in mouse models","volume":"35","author":"L Menalled","year":"2009","journal-title":"Neurobiol Dis"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1111\/j.1460-9568.2007.05307.x","article-title":"The operant serial implicit learning task reveals early onset motor learning deficits in the Hdh knock-in mouse model of Huntington's disease","volume":"25","author":"RC Trueman","year":"2007","journal-title":"Eur J Neurosci"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.bbr.2008.01.020","article-title":"Time course of choice reaction time deficits in the Hdh(Q92) knock-in mouse model of Huntington's disease in the operant serial implicit learning task (SILT)","volume":"189","author":"RC Trueman","year":"2008","journal-title":"Behav Brain Res"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.bbr.2009.05.006","article-title":"Rule learning, visuospatial function and motor performance in the Hdh(Q92) knock-in mouse model of Huntington's disease","volume":"203","author":"RC Trueman","year":"2009","journal-title":"Behav Brain Res"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.brainresbull.2011.03.012","article-title":"Early onset deficits on the delayed alternation task in the Hdh(Q92) knock-in mouse model of Huntington's disease. Brain","volume":"88","author":"RC Trueman","year":"2012","journal-title":"Res Bull"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.brainresbull.2011.10.019","article-title":"Five choice serial reaction time performance in the HdhQ92 mouse model of Huntington's disease. Brain","volume":"88","author":"RC Trueman","year":"2012","journal-title":"Res Bull"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.brainresbull.2010.05.003","article-title":"Longitudinal analysis of the behavioural phenotype in HdhQ92 Huntington's disease knock-in mice. Brain","volume":"88","author":"S Brooks","year":"2012","journal-title":"Res Bull"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.brainresbull.2011.03.013","article-title":"Light and electron microscopic characterization of the evolution of cellular pathology in HdhQ92 Huntington's disease knock-in mice. Brain","volume":"88","author":"Z Bayram-Weston","year":"2012","journal-title":"Res Bull"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"e23647","DOI":"10.1371\/journal.pone.0023647","article-title":"Quantification of Age-Dependent Somatic CAG Repeat Instability in Hdh CAG Knock-In Mice Reveals Different Expansion Dynamics in Striatum and Liver","volume":"6","author":"JM Lee","year":"2011","journal-title":"PLOS ONE"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.nbd.2008.09.014","article-title":"Intergenerational and striatal CAG repeat instability in Huntington's disease knock-in mice involve different DNA repair genes","volume":"33","author":"E Dragileva","year":"2009","journal-title":"Neurobiol Dis"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/nmeth0605-403","article-title":"Introducing the German Mouse Clinic: open access platform for standardized phenotyping","volume":"2","author":"V Gailus-Durner","year":"2005","journal-title":"Nat Methods"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1007\/978-1-59745-471-1_25","article-title":"Systemic first-line phenotyping","volume":"530","author":"V Gailus-Durner","year":"2009","journal-title":"Methods Mol Biol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.ymeth.2010.08.006","article-title":"Mouse phenotyping","volume":"53","author":"H Fuchs","year":"2011","journal-title":"Methods"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1016\/j.neuropsychologia.2006.01.015","article-title":"Episodic memory impairment in Huntington's disease: a meta-analysis","volume":"44","author":"A Montoya","year":"2006","journal-title":"Neuropsychologia"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1176\/jnp.9.4.598","article-title":"Odor identification in Huntington's disease patients and asymptomatic gene carriers","volume":"9","author":"FW Bylsma","year":"1997","journal-title":"J Neuropsychiatry Clin Neurosci"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1017\/S1355617799577035","article-title":"Odor detection, learning, and memory in Huntington's disease","volume":"5","author":"JM Hamilton","year":"1999","journal-title":"J Int Neuropsychol Soc"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1080\/13803390500473746","article-title":"Olfactory functions in asymptomatic carriers of the Huntington disease mutation","volume":"28","author":"M Larsson","year":"2006","journal-title":"J Clin Exp Neuropsychol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.brainres.2007.03.018","article-title":"Olfactory abnormalities in Huntington's disease: decreased plasticity in the primary olfactory cortex of R6\/1 transgenic mice and reduced olfactory discrimination in patients","volume":"1151","author":"SE Lazic","year":"2007","journal-title":"Brain Res"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1097\/WNR.0b013e3280102302","article-title":"Olfaction and neurodegeneration in HD","volume":"18","author":"FA Barrios","year":"2007","journal-title":"Neuroreport"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1136\/jnnp.2007.128728","article-title":"Detection of Huntington's disease decades before diagnosis: the Predict-HD study","volume":"79","author":"JS Paulsen","year":"2008","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref39","first-page":"109","article-title":"High throughput mouse phenotyping","year":"2011"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1212\/01.wnl.0000334276.09729.0e","article-title":"Weight loss in Huntington disease increases with higher CAG repeat number","volume":"71","author":"NA Aziz","year":"2008","journal-title":"Neurology"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1111\/j.1468-1331.2010.02973.x","article-title":"Autonomic symptoms in patients and pre-manifest mutation carriers of Huntington's disease","volume":"17","author":"NA Aziz","year":"2010","journal-title":"Eur J Neurol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1159\/000212174","article-title":"Abnormal glucose tolerance and arginine tolerance tests in Huntington's disease","volume":"23","author":"S Podolsky","year":"1977","journal-title":"Gerontology"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1111\/j.1399-0004.1985.tb00185.x","article-title":"Diabetes mellitus in Huntington disease","volume":"27","author":"LA Farrer","year":"1985","journal-title":"Clin Genet"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1001\/archneur.65.4.476","article-title":"Glucose homeostasis in Huntington disease: abnormalities in insulin sensitivity and early-phase insulin secretion","volume":"65","author":"NM Lali\u0107","year":"2008","journal-title":"Arch Neurol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.tins.2011.06.005","article-title":"Emerging roles for cholesterol in Huntington's disease","volume":"34","author":"M Valenza","year":"2011","journal-title":"Trends Neurosci"},{"key":"ref46","article-title":"Kc P, Dick TE","year":"2010"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1093\/hmg\/8.5.763","article-title":"A Huntington's disease CAG expansion at the murine Hdh locus is unstable and associated with behavioural abnormalities in mice","volume":"8","author":"PF Shelbourne","year":"1999","journal-title":"Hum Mol Genet"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1093\/hmg\/10.2.137","article-title":"Neurological abnormalities in a knock-in mouse model of Huntington's disease","volume":"10","author":"CH Lin","year":"2001","journal-title":"Hum Mol Genet"},{"key":"ref49","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":"ref50","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.brainresbull.2006.02.011","article-title":"Selective extra-dimensional set shifting deficit in a knock-in mouse model of Huntington's disease. Brain","volume":"69","author":"SP Brooks","year":"2006","journal-title":"Res Bull"},{"key":"ref51","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":"ref52","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.neuroscience.2008.08.041","article-title":"Extensive early motor and non-motor behavioral deficits are followed by striatal neuronal loss in knock-in Huntington's disease mice","volume":"157","author":"MA Hickey","year":"2008","journal-title":"Neuroscience"},{"key":"ref53","article-title":"Longitudinal analysis of the behavioural phenotype in Hdh(Q92) Huntington's disease knock-in mice. Brain","author":"S Brooks","year":"2010","journal-title":"Res Bull"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.4161\/auto.6.8.13617","article-title":"Early alterations of autophagy in Huntington disease-like mice","volume":"6","author":"MY Heng","year":"2010","journal-title":"Autophagy"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.expneurol.2010.12.017","article-title":"Longitudinal behavioral, cross-sectional transcriptional and histopathological characterization of a knock-in mouse model of Huntington's disease with 140 CAG repeats","volume":"228","author":"AC Rising","year":"2011","journal-title":"Exp Neurol"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1093\/hmg\/ddr552","article-title":"Long-term memory deficits in Huntington's disease are associated with reduced CBP histone acetylase activity","volume":"21","author":"A Giralt","year":"2012","journal-title":"Hum Mol Genet"},{"key":"ref57","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":"ref58","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.brainresbull.2010.05.004","article-title":"Longitudinal analysis of the behavioural phenotype in Hdh(CAG)150 Huntington's disease knock-in mice. Brain","volume":"88","author":"S Brooks","year":"2012","journal-title":"Res Bull"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"3177","DOI":"10.1093\/hmg\/ddl394","article-title":"Behavioral abnormalities precede neuropathological markers in rats transgenic for Huntington's disease","volume":"15","author":"HP Nguyen","year":"2006","journal-title":"Hum Mol Genet"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/S0006-8993(98)00736-7","article-title":"Striking changes in anxiety in Huntington's disease transgenic mice","volume":"805","author":"SE File","year":"1998","journal-title":"Brain Res"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.neulet.2011.11.063","article-title":"Huntington's disease knock-in male mice show specific anxiety-like behaviour and altered neuronal maturation","volume":"507","author":"S Orvoen","year":"2012","journal-title":"Neurosci Lett"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1093\/brain\/119.5.1633","article-title":"Executive and mnemonic functions in early Huntington's disease","volume":"119","author":"AD Lawrence","year":"1996","journal-title":"Brain"},{"key":"ref63","first-page":"1702","article-title":"Profile of cognitive progression in early Huntington's disease","volume":"61","author":"AK Ho","year":"2003"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1007\/s00415-004-0461-9","article-title":"Cognitive changes in patients with Huntington's disease (HD) and asymptomatic carriers of the HD mutation--a longitudinal follow-up study","volume":"251","author":"J Lemiere","year":"2004","journal-title":"J Neurol"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/S0301-0082(96)00069-X","article-title":"Neural mechanisms of mammalian olfactory learning","volume":"51","author":"PA Brennan","year":"1997","journal-title":"Prog Neurobiol"},{"key":"ref66","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.nlm.2010.09.013","article-title":"Different importance of the volatile and non-volatile fractions of an olfactory signature for individual social recognition in rats versus mice and short-term versus long-term memory","volume":"94","author":"J Noack","year":"2010","journal-title":"Neurobiol Learn Mem"},{"key":"ref67","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s11910-996-0018-7","article-title":"Olfactory dysfunction as a predictor of neurodegenerative disease","volume":"6","author":"MW Albers","year":"2006","journal-title":"Curr Neurol Neurosci Rep"},{"key":"ref68","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nrneurol.2012.80","article-title":"Olfactory dysfunction in Parkinson disease. Nat","volume":"8","author":"RL Doty","year":"2012","journal-title":"Rev Neurol"},{"key":"ref69","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/S0896-6273(00)81209-X","article-title":"Olfactory functions are mediated by parallel and hierarchical processing","volume":"26","author":"I Savic","year":"2000","journal-title":"Neuron"},{"key":"ref70","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.neubiorev.2010.08.004","article-title":"Sniffing out the contributions of the olfactory tubercle to the sense of smell: Hedonics, sensory integration, and more?","volume":"35","author":"DW Wesson","year":"2011","journal-title":"Neurosci Biobehav Rev"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1073\/pnas.97.4.1823","article-title":"Importance of newly generated neurons in the adult olfactory bulb for odor discrimination","volume":"97","author":"G Gheusi","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref72","doi-asserted-by":"crossref","first-page":"3578","DOI":"10.1111\/j.1460-9568.2006.05235.x","article-title":"Neurogenic correlates of an olfactory discrimination task in the adult olfactory bulb","volume":"24","author":"N Mandairon","year":"2006","journal-title":"Eur J Neurosci"},{"key":"ref73","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1038\/nn.3108","article-title":"Activation of adult-born neurons facilitates learning and memory","volume":"15","author":"M Alonso","year":"2012","journal-title":"Nat Neurosci"},{"key":"ref74","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1126\/science.287.5457.1433","article-title":"Mammalian neural stem cells","volume":"287","author":"FH Gage","year":"2000","journal-title":"Science"},{"key":"ref75","doi-asserted-by":"crossref","first-page":"21900","DOI":"10.1073\/pnas.0912171106","article-title":"Impairment of developmental stem cell-mediated striatal neurogenesis and pluripotency genes in a knock-in model of Huntington's disease","volume":"106","author":"AE Molero","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref76","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mcn.2008.06.004","article-title":"Expanded CAG repeats in the murine Huntington's disease gene increases neuronal differentiation of embryonic and neural stem cells","volume":"40","author":"MT Lorincz","year":"2009","journal-title":"Mol Cell Neurosci"},{"key":"ref77","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1097\/00001756-200404090-00014","article-title":"Decreased hippocampal cell proliferation in R6\/1 Huntington's mice","volume":"15","author":"SE Lazic","year":"2004","journal-title":"Neuroreport"},{"key":"ref78","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1111\/j.1460-9568.2006.04715.x","article-title":"Neurogenesis in the R6\/1 transgenic mouse model of Huntington's disease: effects of environmental enrichment","volume":"23","author":"SE Lazic","year":"2006","journal-title":"Eur J Neurosci"},{"key":"ref79","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/j.nbd.2005.05.006","article-title":"Reduced hippocampal neurogenesis in R6\/2 transgenic Huntington's disease mice","volume":"20","author":"JM Gil","year":"2005","journal-title":"Neurobiol Dis"},{"key":"ref80","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.nbd.2010.09.012","article-title":"Altered adult hippocampal neurogenesis in the YAC128 transgenic mouse model of Huntington disease","volume":"41","author":"JM Simpson","year":"2011","journal-title":"Neurobiol Dis"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1016\/j.neuron.2008.10.046","article-title":"Mice with a "monoclonal nose": perturbations in an olfactory map impair odor discrimination","volume":"60","author":"A Fleischmann","year":"2008","journal-title":"Neuron"},{"key":"ref82","doi-asserted-by":"crossref","first-page":"649","DOI":"10.2337\/diabetes.48.3.649","article-title":"Mice transgenic for an expanded CAG repeat in the Huntington's disease gene develop diabetes","volume":"48","author":"MS Hurlbert","year":"1999","journal-title":"Diabetes"},{"key":"ref83","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1111\/j.1365-2826.2007.01629.x","article-title":"Impaired glucose tolerance in the R6\/1 transgenic mouse model of Huntington's disease","volume":"20","author":"K Josefsen","year":"2008","journal-title":"J Neuroendocrinol"},{"key":"ref84","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1111\/j.1365-2826.2009.01898.x","article-title":"Huntington's disease does not appear to increase the risk of diabetes mellitus","volume":"21","author":"TW Boesgaard","year":"2009","journal-title":"J Neuroendocrinol"},{"key":"ref85","doi-asserted-by":"crossref","first-page":"3217","DOI":"10.1172\/JCI24196","article-title":"Increased glucose tolerance and reduced adiposity in the absence of fasting hypoglycemia in mice with liver-specific Gs alpha deficiency","volume":"115","author":"M Chen","year":"2005","journal-title":"J Clin Invest"},{"key":"ref86","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.nbd.2010.08.009","article-title":"Reduced gluconeogenesis and lactate clearance in Huntington's disease","volume":"40","author":"K Josefsen","year":"2010","journal-title":"Neurobiol Dis"},{"key":"ref87","first-page":"151","article-title":"Huntington's chorea. A study of liver function and histology","volume":"42","author":"JM Bolt","year":"1973","journal-title":"Q J Med"},{"key":"ref88","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1093\/hmg\/8.5.813","article-title":"Formation of polyglutamine inclusions in non-CNS tissue","volume":"8","author":"K Sathasivam","year":"1999","journal-title":"Hum Mol Genet"},{"key":"ref89","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":"ref90","doi-asserted-by":"crossref","first-page":"10199","DOI":"10.1523\/JNEUROSCI.1694-10.2010","article-title":"Disruption of peripheral circadian timekeeping in a mouse model of Huntington's disease and its restoration by temporally scheduled feeding","volume":"30","author":"ES Maywood","year":"2010","journal-title":"J Neurosci"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1212\/WNL.0b013e318282514e","article-title":"Hepatic mitochondrial dysfunction in manifest and premanifest Huntington disease","volume":"80","author":"SH St\u00fcwe","year":"2013","journal-title":"Neurology"},{"key":"ref92","doi-asserted-by":"crossref","first-page":"2871","DOI":"10.1093\/hmg\/ddi319","article-title":"HD CAG repeat implicates a dominant property of huntingtin in mitochondrial energy metabolism","volume":"14","author":"IS Seong","year":"2005","journal-title":"Hum Mol Genet"},{"key":"ref93","doi-asserted-by":"crossref","first-page":"4258","DOI":"10.1093\/hmg\/ddr355","article-title":"Differential effects of the Huntington's disease CAG mutation in striatum and cerebellum are quantitative not qualitative","volume":"20","author":"E Fossale","year":"2011","journal-title":"Hum Mol Genet"},{"key":"ref94","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1074\/jbc.M111.309849","article-title":"Early alterations of brain cellular energy homeostasis in Huntington disease models","volume":"287","author":"F Mochel","year":"2012","journal-title":"J Biol Chem"},{"key":"ref95","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1038\/jcbfm.2012.104","article-title":"Homeostatic adaptations in brain energy metabolism in mouse models of Huntington disease","volume":"32","author":"I Tkac","year":"2012","journal-title":"J Cereb Blood Flow Metab"},{"key":"ref96","doi-asserted-by":"crossref","DOI":"10.1371\/currents.RRN1214","article-title":"Body composition in premanifest Huntington's disease reveals lower bone density compared to controls","volume":"3","author":"AO Goodman","year":"2011","journal-title":"PLoS Curr"},{"key":"ref97","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1093\/hmg\/ddl094","article-title":"Progressive alterations in the hypothalamic-pituitary-adrenal axis in the R6\/2 transgenic mouse model of Huntington's disease","volume":"15","author":"M Bj\u00f6rkqvist","year":"2006","journal-title":"Hum Mol Genet"},{"key":"ref98","doi-asserted-by":"crossref","first-page":"777","DOI":"10.3233\/JAD-2009-1185","article-title":"Bone density and brain atrophy in early","volume":"18","author":"N Loskutova","year":"2009","journal-title":"Journal of Alzheimer'S Disease - J Alzheimers Dis"},{"key":"ref99","doi-asserted-by":"crossref","first-page":"313","DOI":"10.3233\/JAD-2010-1364","article-title":"Reduced limbic and hypothalamic volumes correlate with bone density in early","volume":"20","author":"N Loskutova","year":"2010","journal-title":"Journal of Alzheimer'S Disease - J Alzheimers Dis"},{"key":"ref100","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1001\/archneur.56.10.1248","article-title":"Sympathetic skin response and heart rate variability in patients with Huntington disease","volume":"56","author":"KR Sharma","year":"1999","journal-title":"Arch Neurol"},{"key":"ref101","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1136\/jnnp.72.6.726","article-title":"Autonomic nervous system function in Huntington's disease","volume":"72","author":"J Andrich","year":"2002","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref102","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1111\/j.1468-1331.2004.00894.x","article-title":"Early sympathetic hyperactivity in Huntington's disease","volume":"11","author":"J Kobal","year":"2004","journal-title":"Eur J Neurol"},{"key":"ref103","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1111\/j.1468-1331.2008.02173.x","article-title":"Cardiovagal modulation upon postural change is altered in Huntington's disease","volume":"15","author":"KJ B\u00e4r","year":"2008","journal-title":"Eur J Neurol"},{"key":"ref104","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1111\/j.1600-0404.2009.01251.x","article-title":"Autonomic dysfunction in presymptomatic and early symptomatic Huntington's disease","volume":"121","author":"J Kobal","year":"2010","journal-title":"Acta Neurol Scand"},{"key":"ref105","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1007\/s00415-011-6279-3","article-title":"Microcirculation response to local cooling in patients with Huntington's disease","volume":"259","author":"Z Melik","year":"2012","journal-title":"J Neurol"},{"key":"ref106","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.nbd.2006.09.016","article-title":"Cardiac dysfunction in the R6\/2 mouse model of Huntington's disease","volume":"25","author":"MJ Mihm","year":"2007","journal-title":"Neurobiol Dis"},{"key":"ref107","doi-asserted-by":"crossref","DOI":"10.1371\/currents.RRN1266","article-title":"Baroreceptor reflex dysfunction in the BACHD mouse model of Huntington's disease","volume":"3","author":"AM Schroeder","year":"2011","journal-title":"PLoS Curr"},{"key":"ref108","doi-asserted-by":"crossref","first-page":"5845","DOI":"10.1113\/jphysiol.2012.238113","article-title":"Neurocardiac dysregulation and neurogenic arrhythmias in a transgenic mouse model of Huntington's disease","volume":"590","author":"H Kiriazis","year":"2012","journal-title":"J Physiol"},{"key":"ref109","doi-asserted-by":"crossref","first-page":"153","DOI":"10.5694\/j.1326-5377.1982.tb132224.x","article-title":"Causes of death in Huntington's disease","volume":"1","author":"E Chiu","year":"1982","journal-title":"Med J Aust"},{"key":"ref110","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1212\/WNL.38.5.769","article-title":"Huntington's disease mortality in the United States","volume":"38","author":"DJ Lanska","year":"1988","journal-title":"Neurology"},{"key":"ref111","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1016\/S0025-6196(12)62272-1","article-title":"The central autonomic network: functional organization, dysfunction, and perspective","volume":"68","author":"EE Benarroch","year":"1993","journal-title":"Mayo Clin Proc"},{"key":"ref112","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1212\/01.wnl.0000174432.87383.87","article-title":"Regional cortical thinning in preclinical Huntington disease and its relationship to cognition","volume":"65","author":"HD Rosas","year":"2005","journal-title":"Neurology"},{"key":"ref113","first-page":"223","article-title":"Hypothalamic dysfunction and neuroendocrine and metabolic alterations in Huntington's disease: clinical consequences and therapeutic implications","volume":"18","author":"NA Aziz","year":"2007","journal-title":"Rev Neurosci"},{"key":"ref114","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1111\/j.1463-1326.2011.01453.x","article-title":"Brain glucose sensing and neural regulation of insulin and glucagon secretion","volume":"13","author":"B Thorens","year":"2011","journal-title":"Diabetes Obes Metab"},{"key":"ref115","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.bbr.2006.12.004","article-title":"Sex differences in behavior and striatal ascorbate release in the 140 CAG knock-in mouse model of Huntington's disease","volume":"178","author":"JL Dorner","year":"2007","journal-title":"Behav Brain Res"},{"key":"ref116","doi-asserted-by":"crossref","first-page":"e22133","DOI":"10.1371\/journal.pone.0022133","article-title":"Sexually dimorphic serotonergic dysfunction in a mouse model of Huntington's disease and depression","volume":"6","author":"T Renoir","year":"2011","journal-title":"PLOS ONE"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0080923","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,8,10]],"date-time":"2020-08-10T13:31:16Z","timestamp":1597066276000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0080923"}},"subtitle":[],"editor":[{"given":"David\u00a0R","family":"Borchelt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2013,11,22]]},"references-count":116,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2013,11,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0080923","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,11,22]]}}}