ArticleNeuron2015
N17 Modifies mutant Huntingtin nuclear pathogenesis and severity of disease in HD BAC transgenic mice.
Abstract readVideo-Audio Media
In one paragraph
Article in Neuron, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
–field-weighted citation impact
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed.
- Alzheimer's Disease Risk Factor APOE4 Exerts Dimorphic Effects on Female Bone.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Self-inactivating AAV-CRISPR at different ages enables sustained amelioration of Huntington's disease deficits in BAC226Q mice.Science advances · 2026Article
- Prevention of ubiquitination at K6 and K9 in mutant huntingtin exacerbates disease pathology in a knock-in mouse model.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Post-Translational Modifications of Huntingtin: Mechanistic Insights and Therapeutic Opportunities in Huntington's Disease.International journal of molecular sciences · 2025Review
- Cerulenin partially corrects the disrupted developmental transcriptomic signature in Huntington's disease striatal medium spiny neurons.Stem cells (Dayton, Ohio) · 2025Article
- Transient Interdomain Interactions Modulate the Monomeric Structural Ensemble and Self-Assembly of Huntingtin Exon 1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Altered huntingtin-chromatin interactions predict transcriptional and epigenetic changes in Huntington's disease.Disease models & mechanisms · 2025Article
- The N17 domain of huntingtin as a multifaceted player in Huntington's disease.Frontiers in molecular biosciences · 2024Review
- Proteomic analysis of X-linked dystonia parkinsonism disease striatal neurons reveals altered RNA metabolism and splicing.Neurobiology of disease · 2024Article
- Elucidating the Influence of Lipid Composition on Bilayer Perturbations Induced by the N-terminal Region of the Huntingtin Protein.Biophysica · 2023Article
- Review
- VGLUT3 Deletion Rescues Motor Deficits and Neuronal Loss in the zQ175 Mouse Model of Huntington's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Article
- Synaptic Dysfunction in Huntington's Disease: Lessons from Genetic Animal Models.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2022Article
- Mutant huntingtin messenger RNA forms neuronal nuclear clusters in rodent and human brains.Brain communications · 2022Article
- Zebrafish as a model organism for neurodegenerative disease.Frontiers in molecular neuroscience · 2022Review
- Therapeutic reversal of Huntington's disease by in vivo self-assembled siRNAs.Brain : a journal of neurology · 2021Article
- Huntingtin structure is orchestrated by HAP40 and shows a polyglutamine expansion-specific interaction with exon 1.Communications biology · 2021Article
- Fluc-EGFP reporter mice reveal differential alterations of neuronal proteostasis in aging and disease.The EMBO journal · 2021Article
- An Expanded Polyproline Domain Maintains Mutant Huntingtin SolubleFrontiers in molecular neuroscience · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Xiaofeng GuCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Brain Research Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Jeffrey P CantleCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Brain Research Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Erin R GreinerCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
C Y Daniel LeeCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Brain Research Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Albert M BarthDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Fuying GaoCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Chang Sin ParkCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Brain Research Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Zhiqiang ZhangDepartment of Neurology, Washington University School of Medicine St. Louis, MO 63110, USA; Department of Neurology and Neurotherapeutics, University of Texas, Southwestern Medical Center, Dallas, TX 75390, USA.
Susana Sandoval-MillerCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Brain Research Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Richard L ZhangCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Brain Research Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Marc DiamondDepartment of Neurology, Washington University School of Medicine St. Louis, MO 63110, USA; Department of Neurology and Neurotherapeutics, University of Texas, Southwestern Medical Center, Dallas, TX 75390, USA.
Istvan ModyDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Giovanni CoppolaCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Brain Research Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
X William YangCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Brain Research Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: xwyang@mednet.ucla.edu.
Funding
Integrative Center for Neurogenetics and Neurogenomics - OverallP30NS062691 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI COPPOLA, GIOVANNI · 2009 to 2018
$7.4MTraining Grant in Neurobehavioral GeneticsT32NS048004 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BEARDEN, CARRIE E, OPHOFF, ROEL A · 2004 to 2025
$5.8MConditional Mouse Models: Non-cell-antonomous Toxicities in Huntington's DiseaseR01NS049501 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YANG, XIANGDONG WILLIAM · 2004 to 2014
$3.8MComplement-Microglia Interaction in Synaptic Loss and Neurodegeneration in HDR01NS084298 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI STEVENS, BETH ANN, YANG, XIANGDONG WILLIAM · 2014 to 2018
$1.8MValidating NT17 Dependent Mechanisms in Huntington's Disease SuppressionR01NS074312 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YANG, XIANGDONG WILLIAM · 2011 to 2014
$1.4MNINDS NIH HHS P30 NS062691NINDS NIH HHS R01 NS049501NINDS NIH HHS R01NS049501NINDS NIH HHS R01 NS074312NINDS NIH HHS R01NS074312NINDS NIH HHS R01 NS084298NINDS NIH HHS R01NS084298NINDS NIH HHS T32 NS048004
Abstract
The nucleus is a critical subcellular compartment for the pathogenesis of polyglutamine disorders, including Huntington's disease (HD). Recent studies suggest the first 17-amino-acid domain (N17) of mutant huntingtin (mHTT) mediates its nuclear exclusion in cultured cells. Here, we test whether N17 could be a molecular determinant of nuclear mHTT pathogenesis in vivo. BAC transgenic mice expressing mHTT lacking the N17 domain (BACHD-ΔN17) show dramatically accelerated mHTT pathology exclusively in the nucleus, which is associated with HD-like transcriptionopathy. Interestingly, BACHD-ΔN17 mice manifest more overt disease-like phenotypes than the original BACHD mice, including body weight loss, movement deficits, robust striatal neuron loss, and neuroinflammation. Mechanistically, N17 is necessary for nuclear exclusion of small mHTT fragments that are part of nuclear pathology in HD. Together, our study suggests that N17 modifies nuclear pathogenesis and disease severity in HD mice by regulating subcellular localization of known nuclear pathogenic mHTT species.
Indexed as
Age FactorsAnimalsBrainCell NucleolusDisease Models, AnimalFemaleGene Expression RegulationHEK293 CellsHumansHuntingtin ProteinHuntington DiseaseLocomotionMaleMiceMice, TransgenicNerve Tissue ProteinsHtt protein, mouseHuntingtin ProteinNerve Tissue ProteinsNuclear Proteins
Identifiers
What OpenQuestion holds
Textmetadata
LicenceCC BY-NC
Read underepoch 390
Registered trials
None linked
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.