Genomes and Genes
Gene Symbol: Htt
Alias: AI256365, C430023I11Rik, Hdh, IT15, huntingtin, HD protein homolog, Huntington disease gene homolog, huntington disease protein homolog
Publications161 found, 100 shown here
- Mismatch repair gene Msh2 modifies the timing of early disease in Hdh(Q111) striatumVanessa C Wheeler
Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA
Hum Mol Genet 12:273-81. 2003Somatic 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...
- Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic miceL Mangiarini
Division of Medical and Molecular Genetics, UMDS, Guy s Hospital, London, United Kingdom
Cell 87:493-506. 1996..This transgenic model will greatly assist in an eventual understanding of the molecular pathology of HD and may open the way to the testing of intervention strategies...
- Time course of early motor and neuropathological anomalies in a knock-in mouse model of Huntington's disease with 140 CAG repeatsLiliana B Menalled
Department of Neurology, University of California at Los Angeles, Los Angeles, California 90095, USA
J Comp Neurol 465:11-26. 2003Huntington's disease (HD) is caused by an abnormal expansion of CAG repeats in the gene encoding huntingtin. The development of therapies for HD requires preclinical testing of drugs in animal models that reproduce the dysfunction and ..
- Msh2 deficiency prevents in vivo somatic instability of the CAG repeat in Huntington disease transgenic miceK Manley
Wadsworth Center, New York State Department of Health, David Axelrod Institute, Albany, New York, USA
Nat Genet 23:471-3. 1999..9) or an expanded repeat inserted into the endogenous mouse gene Hdh (ref. 10)...
- Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genesChiara Zuccato
Department of Pharmacological Sciences and Center of Excellence on Neurodegenerative Diseases, University of Milano, Via Balzaretti 9, 20133 Milano, Italy
Nat Genet 35:76-83. 2003b>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)...
- The Hdh(Q150/Q150) knock-in mouse model of HD and the R6/2 exon 1 model develop comparable and widespread molecular phenotypesBen Woodman
Department of Medical and Molecular Genetics, King s College London School of Medicine, London, UK
Brain Res Bull 72:83-97. 2007..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 ..
- Neurological abnormalities in a knock-in mouse model of Huntington's diseaseC H Lin
Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Hum Mol Genet 10:137-44. 2001..HD) were made using gene targeting to replace the short CAG repeat of the mouse Huntington's disease gene homolog (HDH:) with CAG repeats within the length range found to cause HD in humans...
- Proteolysis of mutant huntingtin produces an exon 1 fragment that accumulates as an aggregated protein in neuronal nuclei in Huntington diseaseChristian Landles
Department Medical and Molecular Genetics, King s College London School of Medicine, King s College London, London SE1 9RT, United Kingdom
J Biol Chem 285:8808-23. 2010b>Huntingtin proteolysis has been implicated in the molecular pathogenesis of Huntington disease (HD). Despite an intense effort, the identity of the pathogenic smallest N-terminal fragment has not been determined...
- Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutationS W Davies
Department of Anatomy and Developmental Biology, University College London, United Kingdom
Cell 90:537-48. 1997..to (CAG)156 repeat expansions develop pronounced neuronal intranuclear inclusions, containing the proteins huntingtin and ubiquitin, prior to developing a neurological phenotype...
- Systematic behavioral evaluation of Huntington's disease transgenic and knock-in mouse modelsLiliana Menalled
PsychoGenics Inc, Tarrytown, NY 10591, USA
Neurobiol Dis 35:319-36. 2009..Finally, the Hdh(Q111) knock-in mouse on a CD1 background showed very mild deficits...
- Dramatic tissue-specific mutation length increases are an early molecular event in Huntington disease pathogenesisLaura Kennedy
Division of Molecular Genetics, Faculty of Biomedical and Life Scienes, University of Glasgow, Anderson College Complex, 56 Dumbarton Road, Glasgow G11 6NU, UK
Hum Mol Genet 12:3359-67. 2003..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 ..
- Extensive early motor and non-motor behavioral deficits are followed by striatal neuronal loss in knock-in Huntington's disease miceM A Hickey
Department of Neurology, University of California, Los Angeles, David Geffen School of Medicine, Reed Neurological Research Center B114, 710 Westwood Plaza, Los Angeles, CA 90095, USA
Neuroscience 157:280-95. 2008Huntington's disease is a neurodegenerative disorder, caused by an elongation of CAG repeats in the huntingtin gene...
- Length-dependent gametic CAG repeat instability in the Huntington's disease knock-in mouseV C Wheeler
Molecular Neurogenetics Unit, Massachusetts General Hospital East, Building 149, 13th Street, Charlestown, MA 02129, USA
Hum Mol Genet 8:115-22. 1999..A similar pattern was obtained when this repeat was inserted into exon 1 of the mouse Hdh gene...
- Wild-type huntingtin reduces the cellular toxicity of mutant huntingtin in vivoB R Leavitt
Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4
Am J Hum Genet 68:313-24. 2001..yeast artificial chromosome (YAC) transgenic mice expressing normal (YAC18) and mutant (YAC46 or YAC72) human huntingtin (htt), in a developmental- and tissue-specific manner, that is identical to endogenous htt...
- Mutant huntingtin causes metabolic imbalance by disruption of hypothalamic neurocircuitsSofia Hult
Translational Neuroendocrine Research Unit, Department of Experimental Medical Sciences, Lund University, Lund, Sweden
Cell Metab 13:428-39. 2011In Huntington's disease (HD), the mutant huntingtin protein is ubiquitously expressed...
- Huntingtin is required for mitotic spindle orientation and mammalian neurogenesisJuliette D Godin
Institut Curie, Orsay F 91405, France
Neuron 67:392-406. 2010b>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...
- Mitochondrial dysfunction and free radical damage in the Huntington R6/2 transgenic mouseS J Tabrizi
University Department of Clinical Neurosciences, Royal Free and University College Medical School, London, UK
Ann Neurol 47:80-6. 2000..by an abnormally expanded (>36) CAG repeat within the ITI5 gene encoding a widely expressed 349-kd protein, huntingtin. The medium spiny neurons of the caudate preferentially degenerate in Huntington's disease, with the presence of ..
- Genetic background modifies nuclear mutant huntingtin accumulation and HD CAG repeat instability in Huntington's disease knock-in miceAlejandro Lloret
Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA
Hum Mol Genet 15:2015-24. 2006..instability of the HD CAG repeat and the striatal-specific somatic HD CAG repeat expansion, nuclear mutant huntingtin accumulation and intranuclear inclusion formation...
- Inhibition of calpain cleavage of huntingtin reduces toxicity: accumulation of calpain/caspase fragments in the nucleusJuliette Gafni
The Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, California 94945, USA
J Biol Chem 279:20211-20. 2004..HD) is a neurodegenerative disorder caused by a polyglutamine (polyQ) tract expansion near the N terminus of huntingtin (Htt)...
- Progressive phenotype and nuclear accumulation of an amino-terminal cleavage fragment in a transgenic mouse model with inducible expression of full-length mutant huntingtinYuji Tanaka
Division of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, CMSC 8 121, 600 North Wolfe Street, Baltimore, MD 21287, USA
Neurobiol Dis 21:381-91. 2006..disorder characterized behaviorally by chorea, incoordination, and shortened lifespan and neuropathologically by huntingtin inclusions and neuronal degeneration...
- Body weight is modulated by levels of full-length huntingtinJeremy M Van Raamsdonk
Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada V6T 1Z3
Hum Mol Genet 15:1513-23. 2006..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...
- Adipose tissue dysfunction tracks disease progression in two Huntington's disease mouse modelsJack Phan
Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA 90095, USA
Hum Mol Genet 18:1006-16. 2009..gene expression and lipid accumulation in adipocytes can be recapitulated by expression of an inducible mutant huntingtin transgene in an adipocyte cell line and that mutant huntingtin inhibits transcriptional activity of the PGC-..
- Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtinG Schilling
Department of Psychiatry, Division of Neuropathology, Johns Hopkins University, Baltimore, MD 21205 2196, USA
Hum Mol Genet 8:397-407. 1999..an inherited, neurodegenerative disorder caused by the expansion of a glutamine repeat in the N-terminus of the huntingtin protein...
- Dramatic mutation instability in HD mouse striatum: does polyglutamine load contribute to cell-specific vulnerability in Huntington's disease?L Kennedy
Division of Molecular Genetics, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G11 6NU, UK
Hum Mol Genet 9:2539-44. 2000..unstable CAG triplet repeat expansion encoding a polyglutamine stretch within the ubiquitously expressed protein huntingtin is responsible for causing Huntington's disease (HD)...
- Selective extra-dimensional set shifting deficit in a knock-in mouse model of Huntington's diseaseS P Brooks
Cardiff University, Schools of Biological Sciences, Museum Avenue, PO Box 911, Cardiff CF10 3US, Wales, UK
Brain Res Bull 69:452-7. 2006..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 ..
- Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegenerationLibin Cui
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, MassGeneral Institute for Neurodegeneration, Charlestown, MA 02129 USA
Cell 127:59-69. 2006Huntington's disease (HD) is an inherited neurodegenerative disease caused by a glutamine repeat expansion in huntingtin protein. Transcriptional deregulation and altered energy metabolism have been implicated in HD pathogenesis...
- Mutant huntingtin's effects on striatal gene expression in mice recapitulate changes observed in human Huntington's disease brain and do not differ with mutant huntingtin length or wild-type huntingtin dosageAlexandre Kuhn
Ecole Polytechnique Federale de Lausanne EPFL, 1015 Lausanne, Switzerland
Hum Mol Genet 16:1845-61. 2007To test the hypotheses that mutant huntingtin protein length and wild-type huntingtin dosage have important effects on disease-related transcriptional dysfunction, we compared the changes in mRNA in seven genetic mouse models of ..
- A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's diseaseMaria Björkqvist
Neuronal Survival Unit, Department of Experimental Medical Sciences, Wallenberg Neuroscience Center, Lund University, S 221 00 Lund, Sweden
J Exp Med 205:1869-77. 2008..Monocytes from HD subjects expressed mutant huntingtin and were pathologically hyperactive in response to stimulation, suggesting that the mutant protein triggers a ..
- Serines 13 and 16 are critical determinants of full-length human mutant huntingtin induced disease pathogenesis in HD miceXiaofeng Gu
Center for Neurobehavioral Genetics, The Jane and Terry Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA
Neuron 64:828-40. 2009The N-terminal 17 amino acids of huntingtin (NT17) can be phosphorylated on serines 13 and 16; however, the significance of these modifications in Huntington's disease pathogenesis remains unknown...
- In vivo expression of polyglutamine-expanded huntingtin by mouse striatal astrocytes impairs glutamate transport: a correlation with Huntington's disease subjectsMathilde Faideau
CEA, Institute of Biomedical Imaging, Molecular Imaging Research Center, F 92265 Fontenay aux Roses, France
Hum Mol Genet 19:3053-67. 2010..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...
- Wild-type huntingtin ameliorates striatal neuronal atrophy but does not prevent other abnormalities in the YAC128 mouse model of Huntington diseaseJeremy M Van Raamsdonk
Department of Medical Genetics and Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, V5Z 4H4, BC, Canada
BMC Neurosci 7:80. 2006Huntington disease (HD) is an adult onset neurodegenerative disorder caused by a polyglutamine expansion in the huntingtin (htt) protein...
- Human huntingtin derived from YAC transgenes compensates for loss of murine huntingtin by rescue of the embryonic lethal phenotypeJ G Hodgson
Department of Medical Genetics, University of British Columbia, Vancouver, Canada
Hum Mol Genet 5:1875-85. 1996..The HD protein (huntingtin) plays a critical role in early embryonic development since homozygous targeted disruption of the murine HD gene ..
- Age-dependent and tissue-specific CAG repeat instability occurs in mouse knock-in for a mutant Huntington's disease geneH Ishiguro
Institute for Comprehensive Medical Science, Fujita Health University, Toyoake Aichi 470 1192, Japan
J Neurosci Res 65:289-97. 2001..Chimeric proteins composed of human mutated exon 1 and mouse huntingtin are expressed ubiquitously in brain and peripheral tissues...
- Inactivation of Hdh in the brain and testis results in progressive neurodegeneration and sterility in miceI Dragatsis
Department of Genetics and Development, Columbia University, New York, New York, USA
Nat Genet 26:300-6. 2000..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 ..
- Mutant huntingtin directly increases susceptibility of mitochondria to the calcium-induced permeability transition and cytochrome c releaseYeun Su Choo
Department of Psychiatry, University of Alabama at Birmingham, 35294, USA
Hum Mol Genet 13:1407-20. 2004Huntington'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...
- Levels of mutant huntingtin influence the phenotypic severity of Huntington disease in YAC128 mouse modelsRona K Graham
Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4
Neurobiol Dis 21:444-55. 2006..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 ..
- Quantification of age-dependent somatic CAG repeat instability in Hdh CAG knock-in mice reveals different expansion dynamics in striatum and liverJong Min Lee
Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, United States of America
PLoS ONE 6:e23647. 2011Age at onset of Huntington's disease (HD) is largely determined by the CAG trinucleotide repeat length in the HTT gene...
- Targeted inactivation of the mouse Huntington's disease gene homolog HdhM E MacDonald
Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown 02129, USA
Cold Spring Harb Symp Quant Biol 61:627-38. 1996
- Specific progressive cAMP reduction implicates energy deficit in presymptomatic Huntington's disease knock-in miceSilvia Gines
Molecular Neurogenetics Unit, Massachusetts General Hospital, Building 149, 13th St, Charlestown, MA 02129, USA
Hum Mol Genet 12:497-508. 2003..We found that reduced CRE-signaling in Hdh(Q111) striatum, monitored by brain derived neurotrophic factor and phospho-CRE binding protein (CREB), predated ..
- Activation of the IkappaB kinase complex and nuclear factor-kappaB contributes to mutant huntingtin neurotoxicityAli Khoshnan
Biology Division, California Institute of Technology, Pasadena, California 91125, USA
J Neurosci 24:7999-8008. 2004Transcriptional dysregulation by mutant huntingtin (Htt) protein has been implicated in the pathogenesis of Huntington's disease (HD)...
- Contribution of nuclear and extranuclear polyQ to neurological phenotypes in mouse models of Huntington's diseaseCaroline L Benn
King s College London, Medical and Molecular Genetics, GKT School of Medicine, UK
Hum Mol Genet 14:3065-78. 2005In postmortem Huntington's disease brains, mutant htt is present in both nuclear and cytoplasmic compartments...
- N-terminal mutant huntingtin associates with mitochondria and impairs mitochondrial traffickingAdam L Orr
Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia 30322, USA
J Neurosci 28:2783-92. 2008Huntington's disease (HD) is caused by polyglutamine (polyQ) expansion in huntingtin (htt), a large (350 kDa) protein that localizes predominantly to the cytoplasm...
- Impaired TrkB-mediated ERK1/2 activation in huntington disease knock-in striatal cells involves reduced p52/p46 Shc expressionSilvia Gines
Departament de Biologia Cel lular, Facultat de Medicina, Institut d Investigacions Biomediques August Pi i Sunyer, Universitat de Barcelona, Casanova 143, E 08036 Barcelona, Spain
J Biol Chem 285:21537-48. 2010..Altered BDNF-mediated ERK1/2 activation in mutant huntingtin cells is associated with reduced expression of p52/p46 Shc docking proteins...
- The HD mutation causes progressive lethal neurological disease in mice expressing reduced levels of huntingtinW Auerbach
Skirball Institute of Biomolecular Medicine and Howard Hughes Medical Institute, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA
Hum Mol Genet 10:2515-23. 2001b>Huntingtin is an essential protein that with mutant polyglutamine tracts initiates dominant striatal neurodegeneration in Huntington's disease (HD)...
- Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1Mamoru Shibata
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
J Biol Chem 281:14474-85. 2006Intracellular 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)...
- In vivo evidence for NMDA receptor-mediated excitotoxicity in a murine genetic model of Huntington diseaseMary Y Heng
Neuroscience Graduate Program and Department of Neurology, University of Michigan, Ann Arbor, Michigan 48109, USA
J Neurosci 29:3200-5. 2009..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.
- Mouse mutant embryos lacking huntingtin are rescued from lethality by wild-type extraembryonic tissuesI Dragatsis
Department of Genetics, Columbia University, New York, NY 10032, USA
Development 125:1529-39. 1998..nullizygous for a targeted disruption of the Huntington's disease gene homologue (Hdh), which encodes a protein (huntingtin) of unknown biochemical function, become developmentally retarded and disorganized, and die early in development...
- HAP1-huntingtin interactions do not contribute to the molecular pathology in Huntington's disease transgenic miceF Bertaux
Division of Medical and Molecular Genetics, UMDS, Guy s Hospital, London, UK
FEBS Lett 426:229-32. 1998HAP1 (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 ..
- Mice transgenic for an expanded CAG repeat in the Huntington's disease gene develop diabetesM S Hurlbert
Department of Medicine, University of Colorado Health Sciences Center, Denver, USA
Diabetes 48:649-51. 1999..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)...
- Reversal of neuropathology and motor dysfunction in a conditional model of Huntington's diseaseA Yamamoto
Center for Neurobiology and Behavior, Columbia University, New York, New York 10032, USA
Cell 101:57-66. 2000..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...
- Stimulation of NeuroD activity by huntingtin and huntingtin-associated proteins HAP1 and MLK2Edoardo Marcora
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Campus Box 347, Boulder, CO 80309, USA
Proc Natl Acad Sci U S A 100:9578-83. 2003..By using a yeast two-hybrid screen, we identified two proteins that interact with ND, huntingtin-associated protein 1 (HAP1) and mixed-lineage kinase 2 (MLK2), both of which are known to interact with ..
- Mutant huntingtin impairs axonal trafficking in mammalian neurons in vivo and in vitroEugenia Trushina
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo ClinicFoundation, Rochester, Minnesota 55905, USA
Mol Cell Biol 24:8195-209. 2004Recent data in invertebrates demonstrated that huntingtin (htt) is essential for fast axonal trafficking. Here, we provide direct and functional evidence that htt is involved in fast axonal trafficking in mammals...
- Polyglutamine expansion of huntingtin impairs its nuclear exportJonathan Cornett
Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Atlanta, Georgia 30322, USA
Nat Genet 37:198-204. 2005..The mechanism by which mutant huntingtin (htt) accumulates intranuclearly is not known; wild-type htt, a 350-kDa protein of unknown function, is normally ..
- Age-dependent changes in the calcium sensitivity of striatal mitochondria in mouse models of Huntington's DiseaseN Brustovetsky
Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455, USA
J Neurochem 93:1361-70. 2005Striatal and cortical mitochondria from knock-in and transgenic mutant huntingtin mice were examined for their sensitivity to calcium induction of the permeability transition, a cause of mitochondrial depolarization and ATP loss...
- 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 vitroErin B D Clabough
Department of Neuroscience, University of Virginia School of Medicine, PO Box 801392, 409 Lane Road, Charlottesville, VA 22908 1392, USA
Hum Mol Genet 15:607-23. 2006b>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...
- Thermoregulatory and metabolic defects in Huntington's disease transgenic mice implicate PGC-1alpha in Huntington's disease neurodegenerationPatrick Weydt
Department of Laboratory Medicine, University of Washington, Seattle, Washington 98195, USA
Cell Metab 4:349-62. 2006..disease (HD) is a fatal, dominantly inherited disorder caused by polyglutamine repeat expansion in the huntingtin (htt) gene...
- Huntingtin inhibits caspase-3 activationYu Zhang
Neuroapoptosis Laboratory, Department of Neurosurgery, Brigham and Women s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
EMBO J 25:5896-906. 2006Huntington'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...
- Suppression of neuropil aggregates and neurological symptoms by an intracellular antibody implicates the cytoplasmic toxicity of mutant huntingtinChuan En Wang
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA
J Cell Biol 181:803-16. 2008Mutant huntingtin accumulates in the neuronal nuclei and processes, which suggests that its subcellular localization is critical for the pathology of Huntington's disease (HD)...
- Weight loss in Huntington disease increases with higher CAG repeat numberN A Aziz
Leiden University Medical Center, Department of Neurology, Leiden, The Netherlands
Neurology 71:1506-13. 2008..disease (HD) is a hereditary neurodegenerative disorder caused by an expanded number of CAG repeats in the huntingtin gene. A hallmark of HD is unintended weight loss, the cause of which is unknown...
- Distinct conformations of in vitro and in vivo amyloids of huntingtin-exon1 show different cytotoxicityYoko Nekooki-Machida
Tanaka Research Unit, RIKEN Brain Science Institute, Hirosawa 2 1, Wako, Saitama 351 0198, Japan
Proc Natl Acad Sci U S A 106:9679-84. 2009..Here we show that huntingtin-exon1 (thtt) with expanded polyglutamines remarkably misfolds into distinct amyloid conformations under ..
- Increased apoptosis and early embryonic lethality in mice nullizygous for the Huntington's disease gene homologueS Zeitlin
Department of Pathology, Columbia University, New York, New York 10032, USA
Nat Genet 11:155-63. 1995The expansion of CAG triplet repeats in the translated region of the human HD gene, encoding a protein (huntingtin) of unknown function, is a dominant mutation leading to manifestation of Huntington's disease...
- Inactivation of the mouse Huntington's disease gene homolog HdhM P Duyao
Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown 02129, USA
Science 269:407-10. 1995..disease (HD) is a dominant neurodegenerative disorder caused by expansion of a CAG repeat in the gene encoding huntingtin, a protein of unknown function...
- Targeted disruption of the Huntington's disease gene results in embryonic lethality and behavioral and morphological changes in heterozygotesJ Nasir
Department of Medical Genetics, University of British Columbia, Vancouver, Canada
Cell 81:811-23. 1995..To understand its normal function, we have created a targeted disruption in exon 5 of Hdh (Hdhex5), the murine homolog of the HD gene. Homozygotes die before embryonic day 8...
- Huntingtin is required for neurogenesis and is not impaired by the Huntington's disease CAG expansionJ K White
Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown 02129, USA
Nat Genet 17:404-10. 1997..neurodegenerative disorder caused by a CAG repeat expansion that lengthens a glutamine segment in the novel huntingtin protein...
- A Huntington's disease CAG expansion at the murine Hdh locus is unstable and associated with behavioural abnormalities in miceP F Shelbourne
Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA
Hum Mol Genet 8:763-74. 1999..the disease, we introduced an HD-like mutation (an extended stretch of 72-80 CAG repeats) into the endogenous mouse Hdh gene...
- A YAC mouse model for Huntington's disease with full-length mutant huntingtin, cytoplasmic toxicity, and selective striatal neurodegenerationJ G Hodgson
Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada
Neuron 23:181-92. 1999..yeast artificial chromosome (YAC) transgenic mice expressing normal (YAC18) and mutant (YAC46 and YAC72) huntingtin (htt) in a developmental and tissue-specific manner identical to that observed in Huntington's disease (HD)...
- Long glutamine tracts cause nuclear localization of a novel form of huntingtin in medium spiny striatal neurons in HdhQ92 and HdhQ111 knock-in miceV C Wheeler
Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA
Hum Mol Genet 9:503-13. 2000Huntington's disease (HD) is caused by an expanded N-terminal glutamine tract that endows huntingtin with a striatal-selective structural property ultimately toxic to medium spiny neurons...
- Decrease in striatal enkephalin mRNA in mouse models of Huntington's diseaseL Menalled
Department of Neurology and Mental Retardation Center, University of California at Los Angeles School of Medicine, Los Angeles, California 90095, USA
Exp Neurol 162:328-42. 2000..It is caused by the presence of an expanded CAG repeat in the gene encoding huntingtin, a protein of unknown function...
- Polyglutamine length-dependent interaction of Hsp40 and Hsp70 family chaperones with truncated N-terminal huntingtin: their role in suppression of aggregation and cellular toxicityN R Jana
Laboratory for CAG Repeat Diseases, RIKEN Brain Science Institute, Hirosawa, Japan
Hum Mol Genet 9:2009-18. 2000..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 ..
- Huntingtin: an iron-regulated protein essential for normal nuclear and perinuclear organellesP Hilditch-Maguire
Molecular Neurogenetics Unit, Massachusetts General Hospital, Building 149, 13th Street, Charlestown, MA 02129, USA
Hum Mol Genet 9:2789-97. 2000..Huntington's disease (HD), with its selective neuronal cell loss, is caused by an elongated glutamine tract in the huntingtin protein...
- Abnormalities in the functioning of adipocytes from R6/2 mice that are transgenic for the Huntington's disease mutationJ N Fain
Departments of Molecular Sciences and Anatomy and Neurobiology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA
Hum Mol Genet 10:145-52. 2001..These data suggest that the obesity observed at 8-9 weeks in R6/2 mice may stem from a defect in fat breakdown by adipocytes...
- Huntingtin aggregate-associated axonal degeneration is an early pathological event in Huntington's disease miceH Li
Department of Genetics, Emory University School of Medicine, Atlanta, Georgia 30322, USA
J Neurosci 21:8473-81. 2001..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...
- Increased oxidative damage to DNA in a transgenic mouse model of Huntington's diseaseM B Bogdanov
Department of Neurology and Neuroscience, Weill Medical College of Cornell University and New York Presbyterian Hospital, New York, NY 10021, USA
J Neurochem 79:1246-9. 2001..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...
- Increased sensitivity to N-methyl-D-aspartate receptor-mediated excitotoxicity in a mouse model of Huntington's diseaseMelinda M Zeron
Kinsmen Laboratory of Neurological Research, Department of Psychiatry, 221 84, Lund, Sweden
Neuron 33:849-60. 2002..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...
- Early phenotypes that presage late-onset neurodegenerative disease allow testing of modifiers in Hdh CAG knock-in miceVanessa C Wheeler
Molecular Neurogenetics Unit and Molecular Neuropathology, Massachusetts General Hospital, Charlestown, MA 02129, USA
Hum Mol Genet 11:633-40. 2002In Huntington's disease (HD), CAG repeats extend a glutamine tract in huntingtin to initiate the dominant loss of striatal neurons and chorea...
- Lessons from animal models of Huntington's diseaseDavid C Rubinsztein
Dept of Medical Genetics, Cambridge Institute of Medical Research, Wellcome MRC Building, Addenbrooke s Hospital, Hills Road, Cambridge CB2 2XY, UK
Trends Genet 18:202-9. 2002..are translated into an abnormally long polyglutamine tract close to the N-terminus of the HD gene product, huntingtin. Studies in mouse models and human suggest that the mutation is associated with a deleterious gain of function...
- Nuclear-targeting of mutant huntingtin fragments produces Huntington's disease-like phenotypes in transgenic miceGabriele Schilling
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Hum Mol Genet 13:1599-610. 2004Huntington's disease (HD) results from the expansion of a glutamine repeat near the N-terminus of huntingtin (htt)...
- Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubulesLaurent R Gauthier
Unité Mixte de Recherche 146, Centre National de la Recherche Scientifique, Institut Curie, Building 110, Centre Universitaire, 91405 Orsay Cedex, France
Cell 118:127-38. 2004Polyglutamine expansion (polyQ) in the protein huntingtin is pathogenic and responsible for the neuronal toxicity associated with Huntington's disease (HD)...
- Biochemical, ultrastructural, and reversibility studies on huntingtin filaments isolated from mouse and human brainMiguel Diaz-Hernandez
Centro de Biologia Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autonoma de Madrid, 28029 Madrid, Spain
J Neurosci 24:9361-71. 2004..microscopy, both in human and mouse samples, revealed that the stable component of the inclusions are mutant huntingtin-containing and ubiquitin-containing fibrils...
- RNA association and nucleocytoplasmic shuttling by ataxin-1Stuart Irwin
McMaster University, HSC 4H45, Department of Biochemistry, Hamilton, Ontario, L8N 3Z5, Canada
J Cell Sci 118:233-42. 2005..These results suggest that the normal role of ataxin-1 may be in RNA processing, perhaps nuclear RNA export. Thus, nuclear retention of mutant ataxin-1 may be an important toxic gain of function in SCA1 disease...
- Neuronal intranuclear inclusions and neuropil aggregates in HdhCAG(150) knockin miceS J Tallaksen-Greene
Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA
Neuroscience 131:843-52. 2005..Diffuse nuclear localization of huntingtin protein (htt) was noted initially within striatal neurons at approximately 28 weeks, followed by the development ..
- Cognitive dysfunction precedes neuropathology and motor abnormalities in the YAC128 mouse model of Huntington's diseaseJeremy M Van Raamsdonk
Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, V6T 1Z3 Canada
J Neurosci 25:4169-80. 2005....
- Mitochondrial respiration and ATP production are significantly impaired in striatal cells expressing mutant huntingtinTamara Milakovic
Department of Psychiatry, University of Alabama at Birmingham, Birmingham, Alabama 35294 0017, USA
J Biol Chem 280:30773-82. 2005..Nonetheless, the specific mitochondrial defects due to the presence of mutant huntingtin have not been fully elucidated...
- Absence of behavioral abnormalities and neurodegeneration in vivo despite widespread neuronal huntingtin inclusionsElizabeth J Slow
Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada V5Z 4H4
Proc Natl Acad Sci U S A 102:11402-7. 2005We have serendipitously established a mouse that expresses an N-terminal human huntingtin (htt) fragment with an expanded polyglutamine repeat (approximately 120) under the control of the endogenous human promoter (shortstop)...
- Reduced expression of the TrkB receptor in Huntington's disease mouse models and in human brainSilvia Gines
Departament de Biologia Cel lular i Anatomia Patològica, Facultat de Medicina, Universitat de Barcelona, Casanova 143, E 08036 Barcelona, Spain
Eur J Neurosci 23:649-58. 2006..Our findings also demonstrated that continuous expression of mutant huntingtin is required to down-regulate TrkB levels...
- Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtinRona K Graham
Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC V5Z 4H4, Canada
Cell 125:1179-91. 2006Cleavage of huntingtin (htt) has been characterized in vitro, and accumulation of caspase cleavage fragments represents an early pathological change in brains of Huntington's disease (HD) patients...
- Mitochondrial dysfunction in Huntington's disease: the bioenergetics of isolated and in situ mitochondria from transgenic miceJorge M A Oliveira
Buck Institute for Age Research, Novato, California, USA
J Neurochem 101:241-9. 2007..Moreover, moderate expression of full-length mutant huntingtin (in Hdh150 knock-in heterozygotes) does not significantly impair mitochondrial respiration in unstimulated ..
- Huntingtin facilitates dynein/dynactin-mediated vesicle transportJuliane P Caviston
Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Proc Natl Acad Sci U S A 104:10045-50. 2007..b>Huntingtin (Htt) is a vesicle-associated protein found in both neuronal and nonneuronal cells that is thought to be ..
- Huntingtin has a membrane association signal that can modulate huntingtin aggregation, nuclear entry and toxicityRandy Singh Atwal
Department of Biochemistry and Biomedical Sciences, McMaster University, HSC 4H24A, 1200 Main Street West, Hamilton, Ontario, Canada
Hum Mol Genet 16:2600-15. 2007Huntington's disease is caused by an expanded polyglutamine tract in huntingtin protein, leading to accumulation of huntingtin in the nuclei of striatal neurons...
- HAP1 can sequester a subset of TBP in cytoplasmic inclusions via specific interaction with the conserved TBP(CORE)Justin R Prigge
Veterinary Molecular Biology, Molecular Biosciences, Montana State University, 960 Technology Blvd, Bozeman, MT 59717, USA
BMC Mol Biol 8:76. 2007..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...
- Corticostriatal synaptic function in mouse models of Huntington's disease: early effects of huntingtin repeat length and protein loadAusten J Milnerwood
Deptartment of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada
J Physiol 585:817-31. 2007..Furthermore, this study provides a set of neurophysiological sequelae against which to test and compare other mouse models and potential therapies in HD...
- Mutant Huntingtin reduces HSP70 expression through the sequestration of NF-Y transcription factorTomoyuki Yamanaka
Laboratory for Structural Neuropathology, RIKEN Brain Science Institute, Saitama, Japan
EMBO J 27:827-39. 2008In Huntington's disease (HD), mutant Huntingtin, which contains expanded polyglutamine stretches, forms nuclear aggregates in neurons...
- DNA instability in postmitotic neuronsRoman Gonitel
Department of Medical and Molecular Genetics, King s College London School of Medicine, London SE1 9RT, United Kingdom
Proc Natl Acad Sci U S A 105:3467-72. 2008....
- 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)Rebecca C Trueman
School of Biosciences, Cardiff University, Cardiff, Wales, UK
Behav Brain Res 189:317-24. 2008..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 ..
- Huntingtin phosphorylation acts as a molecular switch for anterograde/retrograde transport in neuronsEmilie Colin
Institut Curie, Orsay, France
EMBO J 27:2124-34. 2008..However, the mechanisms that determine the directionality of transport remain unclear. Huntingtin, the protein mutated in Huntington's disease, is a positive regulatory factor for vesicular transport...
- Polyglutamine-modulated striatal calpain activity in YAC transgenic huntington disease mouse model: impact on NMDA receptor function and toxicityCatherine M Cowan
Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3
J Neurosci 28:12725-35. 2008Huntington disease (HD), caused by CAG expansion in the ubiquitously expressed huntingtin gene, is characterized by early dysfunction and death of striatal medium-sized spiny neurons (MSNs)...
- Enhanced sensitivity of striatal neurons to axonal transport defects induced by mutant huntingtinLu Shiun Her
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093, USA
J Neurosci 28:13662-72. 2008..HD) is an autosomal dominant neurodegenerative disease linked to a polyQ (polyglutamine) expansion in the huntingtin protein...
- Acetylation targets mutant huntingtin to autophagosomes for degradationHyunkyung Jeong
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, MassGeneral Institute for Neurodegeneration, Charlestown, MA 02129, USA
Cell 137:60-72. 2009..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 ..
- IKKalpha and IKKbeta regulation of DNA damage-induced cleavage of huntingtinAli Khoshnan
Biology Division 216 76, California Institute of Technology, Pasadena, California, USA
PLoS ONE 4:e5768. 2009Proteolysis 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...
- Alterations in cortical excitation and inhibition in genetic mouse models of Huntington's diseaseDamian M Cummings
Mental Retardation Research Center, David Geffen School of Medicine, Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles, Los Angeles, CA 90095, USA
J Neurosci 29:10371-86. 2009..Furthermore, the differences between synaptic phenotypes in cortex and striatum are important for the development of future therapeutic approaches, which may need to be targeted early in the development of the phenotype...
- Phosphorylation of threonine 3: implications for Huntingtin aggregation and neurotoxicityCharity T Aiken
Department of Developmental and Cell Biology, University of California, Irvine, California 92697, USA
J Biol Chem 284:29427-36. 2009b>Huntingtin (Htt) is a widely expressed protein that causes tissue-specific degeneration when mutated to contain an expanded polyglutamine (poly(Q)) domain...
- Does cortex kill striatum in HD?CHRISTOPHER MEADE; Fiscal Year: 2004An important question in Huntington's disease (HD) pathogenesis is whether mutant huntingtin (Ht) effects striatal cell death directly by perturbing striatal cell fL motion or whether it alters areas outside the striatum (notably cortex) ..
- Neuroprotective Effects of Enhanced Proteasome FunctionBARBARA SNIDER; Fiscal Year: 2006....
- Combination Drug Therapy in Huntington's DiseaseROBERT FERRANTE; Fiscal Year: 2008..neurological disorder caused by an expanded CAG repeat in the gene coding for a protein of unknown function, huntingtin (htt). There is no known treatment for HD...
- BIOPHYSICAL STUDY OF ANTIPSYCHOTICS BEHAVIORAL EFFECTSStephen Fowler; Fiscal Year: 2009..The results will improve our understanding of the pharmacological basis of dopamine related behaviors and assist in the discovery of improved antipsychotic medications. ..
- NMDA RECEPTOR DEVELOPMENT IN NEOSTRIATUMMichael Levine; Fiscal Year: 2001..The outcomes will provide information necessary to understand the role of these receptors in NS development and provide clues for generating rational strategies to treat GluR dysfunction during development and in the adult. ..
- OXIDATIVE INJURY IN PARKINSONS DISEASEROBERT FERRANTE; Fiscal Year: 2002..These studies will have direct relevance to understanding the pathogenesis of PD and to developing new therapies. ..
- 2003 Gordon Conference on CAG Triplet Repeat DisordersMichael Levine; Fiscal Year: 2003..All participants (except speakers and discussants) will be required to present posters. Priority will be given to women, minorities, and persons with disabilities when selecting participants. ..
- 2005 CAG Triplet Repeat Disorders Gordon ConferenceMichael Levine; Fiscal Year: 2005..All participants will be required to present posters. Priority will be given to women, minorities, and persons with disabilities when selecting participants. ..
- Modulation of ataxin-1 phosphorylationHarry Orr; Fiscal Year: 2006..Lead compounds that have been validated will be used to begin preclinical testing using a mouse model of SCA1. ..
- Embryonic Stem Cell Model of Polyglutamine DiseaseMATTHEW LORINCZ; Fiscal Year: 2007..The roles of the normal and mutant HD gene product, huntingtin remain uncertain...
- RECEPTOR GENE TRANSCRIPTION IN HUNTINGTON'S DISEASEJang Ho Cha; Fiscal Year: 2008..Specific Aim 1 will test the hypothesis that mutant huntingtin selectively alters the association of Sp1 with the promoters of genes that are downregulated in HD...
- Neurophysiological Modulation by Dopamine in the NeostriatumMichael Levine; Fiscal Year: 2008..unreadable] [unreadable]..
- Effects of estrogen on neuropathophysiology and behavior in Huntington's diseaseJENELLE DORNER; Fiscal Year: 2008..unreadable] [unreadable] [unreadable] [unreadable]..
- Neuropathology and Pathogenesis of Huntington's DiseaseAnton Reiner; Fiscal Year: 2008..While the mutated huntingtin protein (Htt) that underlies HD pathogenesis appears to interfere with a wide array of cellular functions, the ..