Htt

Summary

Gene Symbol: Htt
Description: huntingtin
Alias: AI256365, C430023I11Rik, Hdh, IT15, huntingtin, HD protein homolog, Huntington disease gene homolog, huntington disease protein homolog
Species: mouse
Products:     Htt

Top Publications

  1. Wheeler V, Lebel L, Vrbanac V, Teed A, te Riele H, MacDonald M. Mismatch repair gene Msh2 modifies the timing of early disease in Hdh(Q111) striatum. Hum Mol Genet. 2003;12:273-81 pubmed
    Somatic instability of expanded HD CAG repeats that encode the polyglutamine tract in mutant huntingtin has been implicated in the striatal selectivity of Huntington's disease (HD) pathology...
  2. Atwal R, Xia J, Pinchev D, Taylor J, Epand R, Truant R. Huntingtin has a membrane association signal that can modulate huntingtin aggregation, nuclear entry and toxicity. Hum Mol Genet. 2007;16:2600-15 pubmed
    Huntington's disease is caused by an expanded polyglutamine tract in huntingtin protein, leading to accumulation of huntingtin in the nuclei of striatal neurons...
  3. Heng M, Detloff P, WANG P, Tsien J, Albin R. In vivo evidence for NMDA receptor-mediated excitotoxicity in a murine genetic model of Huntington disease. J Neurosci. 2009;29:3200-5 pubmed publisher
    ..Our results are consistent with previous suggestions that direct and/or indirect interactions of mutant huntingtin with NMDARs are a proximate cause of neurodegeneration in HD.
  4. Molero A, Gokhan S, Gonzalez S, Feig J, Alexandre L, Mehler M. Impairment of developmental stem cell-mediated striatal neurogenesis and pluripotency genes in a knock-in model of Huntington's disease. Proc Natl Acad Sci U S A. 2009;106:21900-5 pubmed publisher
    ..In fact, we demonstrate that HD knock-in (Hdh-Q111) mice exhibited delayed acquisition of early striatal cytoarchitecture with aberrant expression of progressive ..
  5. Orvoen S, Pla P, Gardier A, Saudou F, David D. Huntington's disease knock-in male mice show specific anxiety-like behaviour and altered neuronal maturation. Neurosci Lett. 2012;507:127-32 pubmed publisher
    ..We report here that knock-in Hdh(Q111) mice, an animal model of HD, that carry an expanded polyglutamine stretch in the mouse HD protein show an ..
  6. Zala D, Hinckelmann M, Yu H, Lyra da Cunha M, Liot G, Cordelières F, et al. Vesicular glycolysis provides on-board energy for fast axonal transport. Cell. 2013;152:479-91 pubmed publisher
    ..GAPDH localizes on vesicles via a huntingtin-dependent mechanism and is transported on fast-moving vesicles within axons...
  7. Gines S, Bosch M, Marco S, Gavalda N, Diaz Hernandez M, Lucas J, et al. Reduced expression of the TrkB receptor in Huntington's disease mouse models and in human brain. Eur J Neurosci. 2006;23:649-58 pubmed
    ..Our findings also demonstrated that continuous expression of mutant huntingtin is required to down-regulate TrkB levels...
  8. Trueman R, Brooks S, Jones L, Dunnett S. 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). Behav Brain Res. 2008;189:317-24 pubmed publisher
    ..We have previously reported that knock-in Hdh(Q92/Q92) mice exhibit a modest impairment in learning the SILT tasks at 4 months of age, prior to the formation of ..
  9. Jeong H, Then F, Melia T, Mazzulli J, Cui L, Savas J, et al. Acetylation targets mutant huntingtin to autophagosomes for degradation. Cell. 2009;137:60-72 pubmed publisher
    ..disease (HD) is an incurable neurodegenerative disease caused by neuronal accumulation of the mutant protein huntingtin. Improving clearance of the mutant protein is expected to prevent cellular dysfunction and neurodegeneration in ..
  10. Ishiguro H, Yamada K, Sawada H, Nishii K, Ichino N, Sawada M, et al. Age-dependent and tissue-specific CAG repeat instability occurs in mouse knock-in for a mutant Huntington's disease gene. J Neurosci Res. 2001;65:289-97 pubmed
    ..Chimeric proteins composed of human mutated exon 1 and mouse huntingtin are expressed ubiquitously in brain and peripheral tissues...

Detail Information

Publications104 found, 100 shown here

  1. Wheeler V, Lebel L, Vrbanac V, Teed A, te Riele H, MacDonald M. Mismatch repair gene Msh2 modifies the timing of early disease in Hdh(Q111) striatum. Hum Mol Genet. 2003;12:273-81 pubmed
    Somatic instability of expanded HD CAG repeats that encode the polyglutamine tract in mutant huntingtin has been implicated in the striatal selectivity of Huntington's disease (HD) pathology...
  2. Atwal R, Xia J, Pinchev D, Taylor J, Epand R, Truant R. Huntingtin has a membrane association signal that can modulate huntingtin aggregation, nuclear entry and toxicity. Hum Mol Genet. 2007;16:2600-15 pubmed
    Huntington's disease is caused by an expanded polyglutamine tract in huntingtin protein, leading to accumulation of huntingtin in the nuclei of striatal neurons...
  3. Heng M, Detloff P, WANG P, Tsien J, Albin R. In vivo evidence for NMDA receptor-mediated excitotoxicity in a murine genetic model of Huntington disease. J Neurosci. 2009;29:3200-5 pubmed publisher
    ..Our results are consistent with previous suggestions that direct and/or indirect interactions of mutant huntingtin with NMDARs are a proximate cause of neurodegeneration in HD.
  4. Molero A, Gokhan S, Gonzalez S, Feig J, Alexandre L, Mehler M. Impairment of developmental stem cell-mediated striatal neurogenesis and pluripotency genes in a knock-in model of Huntington's disease. Proc Natl Acad Sci U S A. 2009;106:21900-5 pubmed publisher
    ..In fact, we demonstrate that HD knock-in (Hdh-Q111) mice exhibited delayed acquisition of early striatal cytoarchitecture with aberrant expression of progressive ..
  5. Orvoen S, Pla P, Gardier A, Saudou F, David D. Huntington's disease knock-in male mice show specific anxiety-like behaviour and altered neuronal maturation. Neurosci Lett. 2012;507:127-32 pubmed publisher
    ..We report here that knock-in Hdh(Q111) mice, an animal model of HD, that carry an expanded polyglutamine stretch in the mouse HD protein show an ..
  6. Zala D, Hinckelmann M, Yu H, Lyra da Cunha M, Liot G, Cordelières F, et al. Vesicular glycolysis provides on-board energy for fast axonal transport. Cell. 2013;152:479-91 pubmed publisher
    ..GAPDH localizes on vesicles via a huntingtin-dependent mechanism and is transported on fast-moving vesicles within axons...
  7. Gines S, Bosch M, Marco S, Gavalda N, Diaz Hernandez M, Lucas J, et al. Reduced expression of the TrkB receptor in Huntington's disease mouse models and in human brain. Eur J Neurosci. 2006;23:649-58 pubmed
    ..Our findings also demonstrated that continuous expression of mutant huntingtin is required to down-regulate TrkB levels...
  8. Trueman R, Brooks S, Jones L, Dunnett S. 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). Behav Brain Res. 2008;189:317-24 pubmed publisher
    ..We have previously reported that knock-in Hdh(Q92/Q92) mice exhibit a modest impairment in learning the SILT tasks at 4 months of age, prior to the formation of ..
  9. Jeong H, Then F, Melia T, Mazzulli J, Cui L, Savas J, et al. Acetylation targets mutant huntingtin to autophagosomes for degradation. Cell. 2009;137:60-72 pubmed publisher
    ..disease (HD) is an incurable neurodegenerative disease caused by neuronal accumulation of the mutant protein huntingtin. Improving clearance of the mutant protein is expected to prevent cellular dysfunction and neurodegeneration in ..
  10. Ishiguro H, Yamada K, Sawada H, Nishii K, Ichino N, Sawada M, et al. Age-dependent and tissue-specific CAG repeat instability occurs in mouse knock-in for a mutant Huntington's disease gene. J Neurosci Res. 2001;65:289-97 pubmed
    ..Chimeric proteins composed of human mutated exon 1 and mouse huntingtin are expressed ubiquitously in brain and peripheral tissues...
  11. Desplats P, Lambert J, Thomas E. Functional roles for the striatal-enriched transcription factor, Bcl11b, in the control of striatal gene expression and transcriptional dysregulation in Huntington's disease. Neurobiol Dis. 2008;31:298-308 pubmed publisher
    ..HD cells, mouse models and human subjects and that overexpression of Bcl11b attenuates toxic effects of mutant huntingtin in cultured striatal neurons...
  12. Nekooki Machida Y, Kurosawa M, Nukina N, Ito K, Oda T, Tanaka M. Distinct conformations of in vitro and in vivo amyloids of huntingtin-exon1 show different cytotoxicity. Proc Natl Acad Sci U S A. 2009;106:9679-84 pubmed publisher
    ..Here we show that huntingtin-exon1 (thtt) with expanded polyglutamines remarkably misfolds into distinct amyloid conformations under ..
  13. Heng M, Duong D, Albin R, Tallaksen Greene S, Hunter J, LESORT M, et al. Early autophagic response in a novel knock-in model of Huntington disease. Hum Mol Genet. 2010;19:3702-20 pubmed publisher
    ..HD mouse model, we provide in vivo evidence of early, sustained alterations of autophagy in response to mutant huntingtin (mhtt)...
  14. Heikkinen T, Lehtimäki K, Vartiainen N, Puoliväli J, Hendricks S, Glaser J, et al. Characterization of neurophysiological and behavioral changes, MRI brain volumetry and 1H MRS in zQ175 knock-in mouse model of Huntington's disease. PLoS ONE. 2012;7:e50717 pubmed publisher
    ..Since the discovery of the huntingtin gene (HTT) mutation that causes the disease, several mouse lines have been developed using different gene ..
  15. Nguyen G, Gokhan S, Molero A, Mehler M. Selective roles of normal and mutant huntingtin in neural induction and early neurogenesis. PLoS ONE. 2013;8:e64368 pubmed publisher
    ..HD) is a neurodegenerative disorder caused by abnormal polyglutamine expansion in the amino-terminal end of the huntingtin protein (Htt) and characterized by progressive striatal and cortical pathology...
  16. Zeron M, Hansson O, Chen N, Wellington C, Leavitt B, Brundin P, et al. Increased sensitivity to N-methyl-D-aspartate receptor-mediated excitotoxicity in a mouse model of Huntington's disease. Neuron. 2002;33:849-60 pubmed
    ..vulnerable to NMDAR-mediated death in a YAC transgenic FVB/N mouse model of HD expressing full-length mutant huntingtin, compared with wild-type FVB/N mice...
  17. Tanaka Y, Igarashi S, Nakamura M, Gafni J, Torcassi C, Schilling G, et al. Progressive phenotype and nuclear accumulation of an amino-terminal cleavage fragment in a transgenic mouse model with inducible expression of full-length mutant huntingtin. Neurobiol Dis. 2006;21:381-91 pubmed
    ..disorder characterized behaviorally by chorea, incoordination, and shortened lifespan and neuropathologically by huntingtin inclusions and neuronal degeneration...
  18. Shibata M, Lu T, Furuya T, Degterev A, Mizushima N, Yoshimori T, et al. Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1. J Biol Chem. 2006;281:14474-85 pubmed
    Intracellular accumulation of mutant Huntingtin with expanded polyglutamine provides a context-dependent cytotoxicity critical for the pathogenesis of Huntington disease (Everett, C. M., and Wood, N. W. (2004) Brain 127, 2385-2405)...
  19. Hickey M, Kosmalska A, Enayati J, Cohen R, Zeitlin S, Levine M, et al. Extensive early motor and non-motor behavioral deficits are followed by striatal neuronal loss in knock-in Huntington's disease mice. Neuroscience. 2008;157:280-95 pubmed publisher
    Huntington's disease is a neurodegenerative disorder, caused by an elongation of CAG repeats in the huntingtin gene...
  20. Seong I, Woda J, Song J, Lloret A, Abeyrathne P, Woo C, et al. Huntingtin facilitates polycomb repressive complex 2. Hum Mol Genet. 2010;19:573-83 pubmed publisher
    Huntington's disease (HD) is caused by expansion of the polymorphic polyglutamine segment in the huntingtin protein...
  21. Lee C, Cantle J, Yang X. Genetic manipulations of mutant huntingtin in mice: new insights into Huntington's disease pathogenesis. FEBS J. 2013;280:4382-94 pubmed publisher
    ..Much of our current knowledge regarding mutant huntingtin (mHtt)-induced disease pathogenesis in mammalian models has been obtained by studying transgenic mouse models ..
  22. Sathasivam K, Lane A, Legleiter J, Warley A, Woodman B, Finkbeiner S, et al. Identical oligomeric and fibrillar structures captured from the brains of R6/2 and knock-in mouse models of Huntington's disease. Hum Mol Genet. 2010;19:65-78 pubmed publisher
    ..isolated from the brains of both mouse models have dimensions identical to those generated from recombinant huntingtin exon 1 proteins...
  23. Song W, Chen J, Petrilli A, Liot G, Klinglmayr E, Zhou Y, et al. Mutant huntingtin binds the mitochondrial fission GTPase dynamin-related protein-1 and increases its enzymatic activity. Nat Med. 2011;17:377-82 pubmed publisher
    ..an inherited and incurable neurodegenerative disorder caused by an abnormal polyglutamine (polyQ) expansion in huntingtin (encoded by HTT)...
  24. Ben M Barek K, Pla P, Orvoen S, Benstaali C, Godin J, Gardier A, et al. Huntingtin mediates anxiety/depression-related behaviors and hippocampal neurogenesis. J Neurosci. 2013;33:8608-20 pubmed publisher
    ..Here, we demonstrate that wild-type huntingtin, the protein mutated in HD, modulates anxiety/depression-related behaviors according to its phosphorylation at ..
  25. Kennedy L, Evans E, Chen C, Craven L, Detloff P, Ennis M, et al. Dramatic tissue-specific mutation length increases are an early molecular event in Huntington disease pathogenesis. Hum Mol Genet. 2003;12:3359-67 pubmed
    ..disease is caused by the expansion of a CAG repeat encoding an extended glutamine tract in a protein called huntingtin. Although the mutant protein is widely expressed, the earliest and most striking neuropathological changes are ..
  26. Trueman R, Brooks S, Jones L, Dunnett S. The operant serial implicit learning task reveals early onset motor learning deficits in the Hdh knock-in mouse model of Huntington's disease. Eur J Neurosci. 2007;25:551-8 pubmed
    ..In the current study, the Hdh(Q92) mouse model of Huntington's disease was examined...
  27. Maywood E, Fraenkel E, McAllister C, Wood N, Reddy A, Hastings M, et al. Disruption of peripheral circadian timekeeping in a mouse model of Huntington's disease and its restoration by temporally scheduled feeding. J Neurosci. 2010;30:10199-204 pubmed publisher
    ..Thus, even subtle imbalances in liver function may exacerbate symptoms of HD, where neurological function is already compromised. ..
  28. Ismailoglu I, Chen Q, Popowski M, Yang L, Gross S, Brivanlou A. Huntingtin protein is essential for mitochondrial metabolism, bioenergetics and structure in murine embryonic stem cells. Dev Biol. 2014;391:230-40 pubmed publisher
    Mutations in the Huntington locus (htt) have devastating consequences. Gain-of-poly-Q repeats in Htt protein causes Huntington's disease (HD), while htt(-/-) mutants display early embryonic lethality...
  29. Andrew S, Goldberg Y, Kremer B, Telenius H, Theilmann J, Adam S, et al. The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington's disease. Nat Genet. 1993;4:398-403 pubmed
    ..Affected HD siblings had significant correlations for trinucleotide expansion (r = 0.66, p < 0.001) which was not apparent for affected parent-child pairs. ..
  30. Fossale E, Wheeler V, Vrbanac V, Lebel L, Teed A, Mysore J, et al. Identification of a presymptomatic molecular phenotype in Hdh CAG knock-in mice. Hum Mol Genet. 2002;11:2233-41 pubmed
    ..of Huntington's disease (HD) is first triggered by a dominant property of the expanded glutamine tract in mutant huntingtin that increases in severity with glutamine size...
  31. Zuccato C, Tartari M, Crotti A, Goffredo D, Valenza M, Conti L, et al. Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes. Nat Genet. 2003;35:76-83 pubmed
    b>Huntingtin protein is mutated in Huntington disease. We previously reported that wild-type but not mutant huntingtin stimulates transcription of the gene encoding brain-derived neurotrophic factor (BDNF; ref. 2)...
  32. Weydt P, Pineda V, Torrence A, Libby R, Satterfield T, Lazarowski E, et al. Thermoregulatory and metabolic defects in Huntington's disease transgenic mice implicate PGC-1alpha in Huntington's disease neurodegeneration. Cell Metab. 2006;4:349-62 pubmed
    ..disease (HD) is a fatal, dominantly inherited disorder caused by polyglutamine repeat expansion in the huntingtin (htt) gene...
  33. Lee J, Pinto R, Gillis T, St Claire J, Wheeler V. Quantification of age-dependent somatic CAG repeat instability in Hdh CAG knock-in mice reveals different expansion dynamics in striatum and liver. PLoS ONE. 2011;6:e23647 pubmed publisher
    Age at onset of Huntington's disease (HD) is largely determined by the CAG trinucleotide repeat length in the HTT gene...
  34. Parker J, Vázquez Manrique R, Tourette C, Farina F, Offner N, Mukhopadhyay A, et al. Integration of ?-catenin, sirtuin, and FOXO signaling protects from mutant huntingtin toxicity. J Neurosci. 2012;32:12630-40 pubmed publisher
    ..Knockdown of ?-catenin enhanced the vulnerability to cell death of mutant-huntingtin striatal cells derived from the HdhQ111 knock-in mice...
  35. Dixon K, Cearley J, Hunter J, Detloff P. Mouse Huntington's disease homolog mRNA levels: variation and allele effects. Gene Expr. 2004;11:221-31 pubmed
    ..to maintain Hdh mRNA levels are not in effect and should not impede therapies designed to destroy mutant huntingtin mRNA...
  36. Godin J, Colombo K, Molina Calavita M, Keryer G, Zala D, Charrin B, et al. Huntingtin is required for mitotic spindle orientation and mammalian neurogenesis. Neuron. 2010;67:392-406 pubmed publisher
    b>Huntingtin is the protein mutated in Huntington's disease, a devastating neurodegenerative disorder. We demonstrate here that huntingtin is essential to control mitosis. Huntingtin is localized at spindle poles during mitosis...
  37. Gauthier L, Charrin B, Borrell Pages M, Dompierre J, Rangone H, Cordelières F, et al. Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules. Cell. 2004;118:127-38 pubmed
    Polyglutamine expansion (polyQ) in the protein huntingtin is pathogenic and responsible for the neuronal toxicity associated with Huntington's disease (HD)...
  38. Prigge J, Schmidt E. HAP1 can sequester a subset of TBP in cytoplasmic inclusions via specific interaction with the conserved TBP(CORE). BMC Mol Biol. 2007;8:76 pubmed
    ..atrophy, and spinocerebellar ataxia 17 (SCA17) are caused by expansions in the polyglutamine (polyQ) repeats in Huntingtin protein (Htt), androgen receptor protein (AR), and TATA-binding protein (TBP), respectively...
  39. Jacobsen J, Gregory G, Woda J, Thompson M, Coser K, Murthy V, et al. HD CAG-correlated gene expression changes support a simple dominant gain of function. Hum Mol Genet. 2011;20:2846-60 pubmed publisher
    Huntington's disease is initiated by the expression of a CAG repeat-encoded polyglutamine region in full-length huntingtin, with dominant effects that vary continuously with CAG size...
  40. Woodman B, Butler R, Landles C, Lupton M, Tse J, Hockly E, et al. The Hdh(Q150/Q150) knock-in mouse model of HD and the R6/2 exon 1 model develop comparable and widespread molecular phenotypes. Brain Res Bull. 2007;72:83-97 pubmed
    ..Of these, mice that are transgenic for an N-terminal huntingtin fragment have been used most extensively because they develop phenotypes with relatively early ages of onset and ..
  41. Lynch G, Kramar E, Rex C, Jia Y, Chappas D, Gall C, et al. Brain-derived neurotrophic factor restores synaptic plasticity in a knock-in mouse model of Huntington's disease. J Neurosci. 2007;27:4424-34 pubmed
    ..Here we show that LTP is impaired in hippocampal slices from presymptomatic Hdh(Q92) and Hdh(Q111) knock-in mice, describe two factors contributing to this deficit, and establish that ..
  42. Aiken C, Steffan J, Guerrero C, Khashwji H, Lukacsovich T, Simmons D, et al. Phosphorylation of threonine 3: implications for Huntingtin aggregation and neurotoxicity. J Biol Chem. 2009;284:29427-36 pubmed publisher
    b>Huntingtin (Htt) is a widely expressed protein that causes tissue-specific degeneration when mutated to contain an expanded polyglutamine (poly(Q)) domain...
  43. Keryer G, Pineda J, Liot G, Kim J, Dietrich P, Benstaali C, et al. Ciliogenesis is regulated by a huntingtin-HAP1-PCM1 pathway and is altered in Huntington disease. J Clin Invest. 2011;121:4372-82 pubmed publisher
    ..It is caused by expansion of a CAG repeat in the first exon of the huntingtin (HTT) gene that encodes a mutant HTT protein with a polyglutamine (polyQ) expansion at the amino terminus...
  44. Yamamoto A, Lucas J, Hen R. Reversal of neuropathology and motor dysfunction in a conditional model of Huntington's disease. Cell. 2000;101:57-66 pubmed
    ..We have created a conditional model of HD by using the tet-regulatable system. Mice expressing a mutated huntingtin fragment demonstrate neuronal inclusions, characteristic neuropathology, and progressive motor dysfunction...
  45. Cornett J, Cao F, Wang C, Ross C, Bates G, Li S, et al. Polyglutamine expansion of huntingtin impairs its nuclear export. Nat Genet. 2005;37:198-204 pubmed
    ..The mechanism by which mutant huntingtin (htt) accumulates intranuclearly is not known; wild-type htt, a 350-kDa protein of unknown function, is normally ..
  46. Milnerwood A, Raymond L. Corticostriatal synaptic function in mouse models of Huntington's disease: early effects of huntingtin repeat length and protein load. J Physiol. 2007;585:817-31 pubmed
    ..Furthermore, this study provides a set of neurophysiological sequelae against which to test and compare other mouse models and potential therapies in HD. ..
  47. Clabough E, Zeitlin S. Deletion of the triplet repeat encoding polyglutamine within the mouse Huntington's disease gene results in subtle behavioral/motor phenotypes in vivo and elevated levels of ATP with cellular senescence in vitro. Hum Mol Genet. 2006;15:607-23 pubmed
    b>Huntingtin (htt), the protein encoded by the Huntington's disease (HD) gene, contains a polymorphic stretch of glutamines (polyQ) near its N-terminus. When the polyQ stretch is expanded beyond 37Q, HD results...
  48. Gines S, Seong I, Fossale E, Ivanova E, Trettel F, Gusella J, et al. Specific progressive cAMP reduction implicates energy deficit in presymptomatic Huntington's disease knock-in mice. Hum Mol Genet. 2003;12:497-508 pubmed
    ..We found that reduced CRE-signaling in Hdh(Q111) striatum, monitored by brain derived neurotrophic factor and phospho-CRE binding protein (CREB), predated ..
  49. Baldo B, Weiss A, Parker C, Bibel M, Paganetti P, Kaupmann K. A screen for enhancers of clearance identifies huntingtin as a heat shock protein 90 (Hsp90) client protein. J Biol Chem. 2012;287:1406-14 pubmed publisher
    Mechanisms to reduce the cellular levels of mutant huntingtin (mHtt) provide promising strategies for treating Huntington disease (HD)...
  50. Marcellin D, Abramowski D, Young D, Richter J, Weiss A, Marcel A, et al. Fragments of HdhQ150 mutant huntingtin form a soluble oligomer pool that declines with aggregate deposition upon aging. PLoS ONE. 2012;7:e44457 pubmed publisher
    Cleavage of the full-length mutant huntingtin (mhtt) protein into smaller, soluble aggregation-prone mhtt fragments appears to be a key process in the neuropathophysiology of Huntington's Disease (HD)...
  51. Karpuj M, Becher M, Springer J, Chabas D, Youssef S, Pedotti R, et al. Prolonged survival and decreased abnormal movements in transgenic model of Huntington disease, with administration of the transglutaminase inhibitor cystamine. Nat Med. 2002;8:143-9 pubmed
    An expanded polyglutamine domain in huntingtin underlies the pathogenic events in Huntington disease (HD), characterized by chorea, dementia and severe weight loss, culminating in death...
  52. Lorincz M, Zawistowski V. Expanded CAG repeats in the murine Huntington's disease gene increases neuronal differentiation of embryonic and neural stem cells. Mol Cell Neurosci. 2009;40:1-13 pubmed publisher
  53. Rozas J, G mez S nchez L, Tom s Zapico C, Lucas J, Fern ndez Chac n R. Increased neurotransmitter release at the neuromuscular junction in a mouse model of polyglutamine disease. J Neurosci. 2011;31:1106-13 pubmed publisher
    ..disease (HD), the expansion of polyglutamine (polyQ) repeats at the N terminus of the ubiquitous protein huntingtin (htt) leads to neurodegeneration in specific brain areas...
  54. Zhang Y, Leavitt B, Van Raamsdonk J, Dragatsis I, Goldowitz D, MacDonald M, et al. Huntingtin inhibits caspase-3 activation. EMBO J. 2006;25:5896-906 pubmed
    Huntington's disease results from a mutation in the HD gene encoding for the protein huntingtin. The function of huntingtin, although beginning to be elucidated, remains largely unclear...
  55. Orr A, Li S, Wang C, Li H, Wang J, Rong J, et al. N-terminal mutant huntingtin associates with mitochondria and impairs mitochondrial trafficking. J Neurosci. 2008;28:2783-92 pubmed publisher
    Huntington's disease (HD) is caused by polyglutamine (polyQ) expansion in huntingtin (htt), a large (350 kDa) protein that localizes predominantly to the cytoplasm...
  56. Hurlbert M, Zhou W, Wasmeier C, Kaddis F, Hutton J, Freed C. Mice transgenic for an expanded CAG repeat in the Huntington's disease gene develop diabetes. Diabetes. 1999;48:649-51 pubmed
    ..syndrome of Huntington's disease has been modeled in transgenic mice by the expression of a portion of the human huntingtin gene together with 140 CAG repeats (the R6/2 strain)...
  57. Miller J, Yates B, Al Ramahi I, Berman A, Sanhueza M, Kim E, et al. A genome-scale RNA-interference screen identifies RRAS signaling as a pathologic feature of Huntington's disease. PLoS Genet. 2012;8:e1003042 pubmed publisher
    A genome-scale RNAi screen was performed in a mammalian cell-based assay to identify modifiers of mutant huntingtin toxicity...
  58. Li H, Li S, Yu Z, Shelbourne P, Li X. Huntingtin aggregate-associated axonal degeneration is an early pathological event in Huntington's disease mice. J Neurosci. 2001;21:8473-81 pubmed
    ..Here we report that in mice expressing full-length mutant huntingtin and modeling early stages of HD, neuropil aggregates form preferentially in the LGP and SN...
  59. Dragatsis I, Levine M, Zeitlin S. Inactivation of Hdh in the brain and testis results in progressive neurodegeneration and sterility in mice. Nat Genet. 2000;26:300-6 pubmed
    ..On the basis of these results, we propose that huntingtin is required for neuronal function and survival in the brain and that a loss-of-function mechanism may contribute ..
  60. Khoshnan A, Ko J, Tescu S, Brundin P, Patterson P. IKKalpha and IKKbeta regulation of DNA damage-induced cleavage of huntingtin. PLoS ONE. 2009;4:e5768 pubmed publisher
    Proteolysis of huntingtin (Htt) plays a key role in the pathogenesis of Huntington's disease (HD). However, the environmental cues and signaling pathways that regulate Htt proteolysis are poorly understood...
  61. Hult S, Soylu R, Bjorklund T, Belgardt B, Mauer J, Bruning J, et al. Mutant huntingtin causes metabolic imbalance by disruption of hypothalamic neurocircuits. Cell Metab. 2011;13:428-439 pubmed publisher
    In Huntington's disease (HD), the mutant huntingtin protein is ubiquitously expressed...
  62. Jana N, Tanaka M, Wang G, Nukina N. Polyglutamine length-dependent interaction of Hsp40 and Hsp70 family chaperones with truncated N-terminal huntingtin: their role in suppression of aggregation and cellular toxicity. Hum Mol Genet. 2000;9:2009-18 pubmed
    ..is an autosomal dominant neurodegenerative disorder caused by polyglutamine expansion in the disease protein, huntingtin. In HD patients and transgenic mice, the affected neurons form characteristic ubiquitin-positive nuclear ..
  63. Fossale E, Seong I, Coser K, Shioda T, Kohane I, Wheeler V, et al. Differential effects of the Huntington's disease CAG mutation in striatum and cerebellum are quantitative not qualitative. Hum Mol Genet. 2011;20:4258-67 pubmed publisher
    ..striatum, whereas the cerebellum is relatively spared despite the ubiquitous expression of full-length mutant huntingtin, implying that inherent tissue-specific differences determine susceptibility to the HD CAG mutation...
  64. Nagaoka U, Kim K, Jana N, Doi H, Maruyama M, Mitsui K, et al. Increased expression of p62 in expanded polyglutamine-expressing cells and its association with polyglutamine inclusions. J Neurochem. 2004;91:57-68 pubmed
    ..is a progressive neurodegenerative disorder that is associated with a CAG repeat expansion in the gene encoding huntingtin. We found that a 60-kDa protein was increased in Neuro2a cells expressing the N-terminal portion of huntingtin ..
  65. Graham R, Slow E, Deng Y, Bissada N, Lu G, Pearson J, et al. Levels of mutant huntingtin influence the phenotypic severity of Huntington disease in YAC128 mouse models. Neurobiol Dis. 2006;21:444-55 pubmed
    ..Neuropathological changes include the appearance of N-terminal huntingtin fragments, decreased brain weight and apoptotic neuronal loss in a select subset of neurons located in the ..
  66. Southwell A, Warby S, Carroll J, Doty C, Skotte N, Zhang W, et al. A fully humanized transgenic mouse model of Huntington disease. Hum Mol Genet. 2013;22:18-34 pubmed publisher
    Silencing the mutant huntingtin gene (muHTT) is a direct and simple therapeutic strategy for the treatment of Huntington disease (HD) in principle...
  67. Mielcarek M, Inuabasi L, Bondulich M, Muller T, Osborne G, Franklin S, et al. Dysfunction of the CNS-heart axis in mouse models of Huntington's disease. PLoS Genet. 2014;10:e1004550 pubmed publisher
    ..Given that huntingtin is ubiquitously expressed, cardiomyocytes may be at risk of an HD-related dysfunction...
  68. Bogdanov M, Andreassen O, Dedeoglu A, Ferrante R, Beal M. Increased oxidative damage to DNA in a transgenic mouse model of Huntington's disease. J Neurochem. 2001;79:1246-9 pubmed
    ..Immunocytochemistry showed increased OH(8)dG staining in late stages of the illness. These results suggest that oxidative damage may play a role in the pathogenesis of neuronal degeneration in the R6/2 transgenic mouse model of HD. ..
  69. Moffitt H, McPhail G, Woodman B, Hobbs C, Bates G. Formation of polyglutamine inclusions in a wide range of non-CNS tissues in the HdhQ150 knock-in mouse model of Huntington's disease. PLoS ONE. 2009;4:e8025 pubmed publisher
    ..expansion in the ubiquitously expressed HD gene resulting in an abnormally long polyglutamine repeat in the huntingtin protein. Polyglutamine inclusions are a hallmark of the neuropathology of HD...
  70. White J, Auerbach W, Duyao M, Vonsattel J, Gusella J, Joyner A, et al. Huntingtin is required for neurogenesis and is not impaired by the Huntington's disease CAG expansion. Nat Genet. 1997;17:404-10 pubmed
    ..neurodegenerative disorder caused by a CAG repeat expansion that lengthens a glutamine segment in the novel huntingtin protein...
  71. Lo Sardo V, Zuccato C, Gaudenzi G, Vitali B, Ramos C, Tartari M, et al. An evolutionary recent neuroepithelial cell adhesion function of huntingtin implicates ADAM10-Ncadherin. Nat Neurosci. 2012;15:713-21 pubmed publisher
    The Huntington's disease gene product, huntingtin, is indispensable for neural tube formation, but its role is obscure...
  72. Feng Z, Jin S, Zupnick A, Hoh J, de Stanchina E, Lowe S, et al. p53 tumor suppressor protein regulates the levels of huntingtin gene expression. Oncogene. 2006;25:1-7 pubmed
    ..The accumulation of the mutant huntingtin protein with an expanded polyglutamine tract plays a central role in the pathology of human Huntington's disease...
  73. Yamanaka T, Miyazaki H, Oyama F, Kurosawa M, Washizu C, Doi H, et al. Mutant Huntingtin reduces HSP70 expression through the sequestration of NF-Y transcription factor. EMBO J. 2008;27:827-39 pubmed publisher
    In Huntington's disease (HD), mutant Huntingtin, which contains expanded polyglutamine stretches, forms nuclear aggregates in neurons...
  74. Reiner A, Del Mar N, Meade C, Yang H, Dragatsis I, Zeitlin S, et al. Neurons lacking huntingtin differentially colonize brain and survive in chimeric mice. J Neurosci. 2001;21:7608-19 pubmed
    To determine whether neurons lacking huntingtin can participate in development and survive in postnatal brain, we used two approaches in an effort to create mice consisting of wild-type cells and cells without huntingtin...
  75. Li X, Valencia A, Sapp E, Masso N, Alexander J, Reeves P, et al. Aberrant Rab11-dependent trafficking of the neuronal glutamate transporter EAAC1 causes oxidative stress and cell death in Huntington's disease. J Neurosci. 2010;30:4552-61 pubmed publisher
    ..Thus, other mechanisms may account for the earliest source of oxidative stress caused by endogenous mutant huntingtin. Here, we report that decreased levels of a major intracellular antioxidant glutathione coincide with ..
  76. Sathasivam K, Hobbs C, Turmaine M, Mangiarini L, Mahal A, Bertaux F, et al. Formation of polyglutamine inclusions in non-CNS tissue. Hum Mol Genet. 1999;8:813-22 pubmed
  77. Van Raamsdonk J, Pearson J, Slow E, Hossain S, Leavitt B, Hayden M. Cognitive dysfunction precedes neuropathology and motor abnormalities in the YAC128 mouse model of Huntington's disease. J Neurosci. 2005;25:4169-80 pubmed
  78. Faideau M, Kim J, Cormier K, Gilmore R, Welch M, Auregan G, et al. In vivo expression of polyglutamine-expanded huntingtin by mouse striatal astrocytes impairs glutamate transport: a correlation with Huntington's disease subjects. Hum Mol Genet. 2010;19:3053-67 pubmed publisher
    ..disorder previously thought to be of primary neuronal origin, despite ubiquitous expression of mutant huntingtin (mHtt). We tested the hypothesis that mHtt expressed in astrocytes may contribute to the pathogenesis of HD...
  79. Brooks S, Betteridge H, Trueman R, Jones L, Dunnett S. Selective extra-dimensional set shifting deficit in a knock-in mouse model of Huntington's disease. Brain Res Bull. 2006;69:452-7 pubmed
    ..The aim of the present paper then, was to test whether homozygous knock-in mice derived from the Hdh(CAG(150)) mouse line were impaired in any of five 2-choice discrimination tasks (simple, compound, compound ..
  80. Bradford J, Shin J, Roberts M, Wang C, Li X, Li S. Expression of mutant huntingtin in mouse brain astrocytes causes age-dependent neurological symptoms. Proc Natl Acad Sci U S A. 2009;106:22480-5 pubmed publisher
    Huntington disease (HD) is an inherited neurological disorder caused by a polyglutamine expansion in the protein huntingtin and is characterized by selective neurodegeneration that preferentially occurs in striatal medium spiny neurons...
  81. O Kusky J, Nasir J, Cicchetti F, Parent A, Hayden M. Neuronal degeneration in the basal ganglia and loss of pallido-subthalamic synapses in mice with targeted disruption of the Huntington's disease gene. Brain Res. 1999;818:468-79 pubmed
    ..These findings show that loss of an intact huntingtin protein is associated with significant morphological alterations in the basal ganglia of adult mice, indicating ..
  82. Choo Y, Johnson G, MacDonald M, Detloff P, Lesort M. Mutant huntingtin directly increases susceptibility of mitochondria to the calcium-induced permeability transition and cytochrome c release. Hum Mol Genet. 2004;13:1407-20 pubmed
    Huntington's disease (HD) is initiated by an abnormally expanded polyglutamine stretch in the huntingtin protein, conferring a novel property on the protein that leads to the loss of striatal neurons...
  83. Benn C, Sun T, Sadri Vakili G, McFarland K, DiRocco D, Yohrling G, et al. Huntingtin modulates transcription, occupies gene promoters in vivo, and binds directly to DNA in a polyglutamine-dependent manner. J Neurosci. 2008;28:10720-33 pubmed publisher
    ..Huntington's disease, a fatal neurodegenerative disorder associated with polyglutamine (polyQ) expansion in the huntingtin (Htt) protein...
  84. Van Raamsdonk J, Gibson W, Pearson J, Murphy Z, Lu G, Leavitt B, et al. Body weight is modulated by levels of full-length huntingtin. Hum Mol Genet. 2006;15:1513-23 pubmed
    ..is an adult-onset neurodegenerative disorder that is caused by the expansion of a polyglutamine tract within the Huntingtin (htt) protein. Wild-type htt has been shown to be involved in transcription, transport and cell survival...
  85. Trueman R, Dunnett S, Jones L, Brooks S. Five choice serial reaction time performance in the HdhQ92 mouse model of Huntington's disease. Brain Res Bull. 2012;88:163-70 pubmed publisher
    ..Various facets of attention have been reported to be affected in Huntington's disease patients, and the Hdh(Q92/Q92) mice have been shown to have deficits on operant tasks which have attentional components...
  86. Menalled L, Kudwa A, Miller S, Fitzpatrick J, Watson Johnson J, Keating N, et al. Comprehensive behavioral and molecular characterization of a new knock-in mouse model of Huntington's disease: zQ175. PLoS ONE. 2012;7:e49838 pubmed publisher
    ..responsible for the disease was identified as an unstable expansion of CAG repeats in the gene encoding the huntingtin protein in 1993, numerous mouse models of HD have been generated to study disease pathogenesis and evaluate ..
  87. Gafni J, Hermel E, Young J, Wellington C, Hayden M, Ellerby L. Inhibition of calpain cleavage of huntingtin reduces toxicity: accumulation of calpain/caspase fragments in the nucleus. J Biol Chem. 2004;279:20211-20 pubmed
    ..HD) is a neurodegenerative disorder caused by a polyglutamine (polyQ) tract expansion near the N terminus of huntingtin (Htt)...
  88. Guidetti P, Bates G, Graham R, Hayden M, Leavitt B, MacDonald M, et al. Elevated brain 3-hydroxykynurenine and quinolinate levels in Huntington disease mice. Neurobiol Dis. 2006;23:190-7 pubmed
    ..increased in the striatum and cortex of the full-length HD models, beginning at 8 months (YAC128) and 15 months (Hdh(Q92) and Hdh(Q111)), respectively...
  89. Gonitel R, Moffitt H, Sathasivam K, Woodman B, Detloff P, Faull R, et al. DNA instability in postmitotic neurons. Proc Natl Acad Sci U S A. 2008;105:3467-72 pubmed publisher
  90. Bertaux F, Sharp A, Ross C, Lehrach H, Bates G, Wanker E. HAP1-huntingtin interactions do not contribute to the molecular pathology in Huntington's disease transgenic mice. FEBS Lett. 1998;426:229-32 pubmed
    HAP1 (huntingtin associated protein) has previously been found to interact with huntingtin (htt) in a glutamine length dependent manner and has been proposed to play a role in the cell specific neurodegeneration observed in Huntington's ..
  91. Her L, Goldstein L. Enhanced sensitivity of striatal neurons to axonal transport defects induced by mutant huntingtin. J Neurosci. 2008;28:13662-72 pubmed publisher
    ..HD) is an autosomal dominant neurodegenerative disease linked to a polyQ (polyglutamine) expansion in the huntingtin protein...
  92. Lundh S, Soylu R, Petersen A. Expression of mutant huntingtin in leptin receptor-expressing neurons does not control the metabolic and psychiatric phenotype of the BACHD mouse. PLoS ONE. 2012;7:e51168 pubmed publisher
    ..manifestation of Huntington's disease (HD), a neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin (HTT) gene...