Evidence map›Paper›PMID 26900923›Full record

ArticleNature neuroscience2016

Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice.

Peter Langfelder, Jeffrey P Cantle, Doxa Chatzopoulou, Nan Wang, Fuying Gao, Ismael Al-Ramahi, Xiao-Hong Lu, Eliana Marisa Ramos, Karla El-Zein, Yining Zhao and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 238 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
238citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

238 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
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  13. Decoding neurodegeneration one cell at a time.The Journal of clinical investigation · 2026
    Review
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178 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors.

Peter LangfelderDepartment of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, California, USA.
Jeffrey P CantleCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience &Human Behavior, University of California, Los Angeles, Los Angeles, California, USA.
Doxa ChatzopoulouCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience &Human Behavior, University of California, Los Angeles, Los Angeles, California, USA.
Nan WangCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience &Human Behavior, University of California, Los Angeles, Los Angeles, California, USA.
Fuying GaoCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience &Human Behavior, University of California, Los Angeles, Los Angeles, California, USA.
Ismael Al-RamahiDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Xiao-Hong LuCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience &Human Behavior, University of California, Los Angeles, Los Angeles, California, USA.
Eliana Marisa RamosCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience &Human Behavior, University of California, Los Angeles, Los Angeles, California, USA.
Karla El-ZeinDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Yining ZhaoCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience &Human Behavior, University of California, Los Angeles, Los Angeles, California, USA.
Sandeep DeverasettyCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience &Human Behavior, University of California, Los Angeles, Los Angeles, California, USA.
Andreas TebbeEvotec Munich GmbH, Martinsried, Germany.
Christoph SchaabEvotec Munich GmbH, Martinsried, Germany.
Daniel J LaveryCHDI Foundation/CHDI Management Inc., Princeton, New Jersey, USA.
David HowlandCHDI Foundation/CHDI Management Inc., Princeton, New Jersey, USA.
Seung KwakCHDI Foundation/CHDI Management Inc., Princeton, New Jersey, USA.
Juan BotasDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Jeffrey S AaronsonCHDI Foundation/CHDI Management Inc., Princeton, New Jersey, USA.
Jim RosinskiCHDI Foundation/CHDI Management Inc., Princeton, New Jersey, USA.
Giovanni CoppolaCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience &Human Behavior, University of California, Los Angeles, Los Angeles, California, USA.ORCID http://orcid.org/0000-0003-2105-1061
Steve HorvathDepartment of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, California, USA.
X William YangCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience &Human Behavior, University of California, Los Angeles, Los Angeles, California, USA.

Funding

Integrative Center for Neurogenetics and Neurogenomics - OverallP30NS062691 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI COPPOLA, GIOVANNI · 2009 to 2018
$7.4M
Conditional Mouse Models: Non-cell-antonomous Toxicities in Huntington's DiseaseR01NS049501 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YANG, XIANGDONG WILLIAM · 2004 to 2014
$3.8M
Complement-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
$1.8M
Validating NT17 Dependent Mechanisms in Huntington's Disease SuppressionR01NS074312 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YANG, XIANGDONG WILLIAM · 2011 to 2014
$1.4M
NINDS NIH HHS P30 NS062691NINDS NIH HHS R01 NS049501NINDS NIH HHS R01NS049501NINDS NIH HHS R01 NS074312NINDS NIH HHS R01NS074312NINDS NIH HHS R01 NS084298NINDS NIH HHS R01NS084298
6 · The paper itself

Abstract

To gain insight into how mutant huntingtin (mHtt) CAG repeat length modifies Huntington's disease (HD) pathogenesis, we profiled mRNA in over 600 brain and peripheral tissue samples from HD knock-in mice with increasing CAG repeat lengths. We found repeat length-dependent transcriptional signatures to be prominent in the striatum, less so in cortex, and minimal in the liver. Coexpression network analyses revealed 13 striatal and 5 cortical modules that correlated highly with CAG length and age, and that were preserved in HD models and sometimes in patients. Top striatal modules implicated mHtt CAG length and age in graded impairment in the expression of identity genes for striatal medium spiny neurons and in dysregulation of cyclic AMP signaling, cell death and protocadherin genes. We used proteomics to confirm 790 genes and 5 striatal modules with CAG length-dependent dysregulation at the protein level, and validated 22 striatal module genes as modifiers of mHtt toxicities in vivo.

Indexed as

AnimalsCerebral CortexCorpus StriatumFemaleGene Knock-In TechniquesGene Regulatory NetworksGenomicsHuntingtin ProteinMaleMiceMice, Inbred C57BLNerve Tissue ProteinsNuclear ProteinsProteomicsHtt protein, mouseHuntingtin ProteinNerve Tissue ProteinsNuclear Proteins

Identifiers

PMID26900923
PMCPMC5984042

What OpenQuestion holds

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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.