Evidence map›Paper›PMID 29843246›Full record

ArticleJournal of Huntington's disease2018

Striatal Mutant Huntingtin Protein Levels Decline with Age in Homozygous Huntington's Disease Knock-In Mouse Models.

Nicholas R Franich, Manuela Basso, Emily A André, Joseph Ochaba, Amit Kumar, Soe Thein, Gianna Fote, Marketta Kachemov, Alice L Lau, Sylvia Y Yeung and 5 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of Huntington's disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
1.2field-weighted citation impact, top 25% of its field
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

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.

  1. Guideline
  2. Article
  3. Review
  4. Review
  5. Huntingtin contains an ubiquitin-binding domain and regulates lysosomal targeting of mitochondrial and RNA-binding proteins.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. IKKβ slows Huntington's disease progression in R6/1 mice.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  13. Article
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

15 authors at 6 institutions in 2 countries.

Nicholas R FranichDepartment of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Manuela BassoCentre for Integrative Biology, University of Trento, Trento, Italy.
Emily A AndréDepartment of Neuroscience, University of Virginia School of Medicine, Charlottesville, VA, USA.
Joseph OchabaDepartment of Neurobiology and Behavior, University of California, Irvine, Irvine, CA, USA.
Amit KumarBurke Medical Research Institute, White Plains, NY, USA.
Soe TheinDepartment of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA.
Gianna FoteDepartment of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA.
Marketta KachemovDepartment of Neurobiology and Behavior, University of California, Irvine, Irvine, CA, USA.
Alice L LauDepartment of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA.
Sylvia Y YeungDepartment of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA.
Alexander OsmandDepartment of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, TN, USA.
Scott O ZeitlinDepartment of Neuroscience, University of Virginia School of Medicine, Charlottesville, VA, USA.
Rajiv R RatanBurke Medical Research Institute, White Plains, NY, USA.
Leslie M ThompsonDepartment of Neurobiology and Behavior, University of California, Irvine, Irvine, CA, USA.
Joan S SteffanDepartment of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA.
University of California, Irvine · USCornell University · USUniversity of Virginia · USUniversity of California, Los Angeles · USUniversity of Tennessee at Knoxville · USUniversity of Trento · IT

Funding

TRANSCRIPTIONAL RESPONSES TO MITOCHONDRIAL DYSFUNCTIONP01AG014930 · NIA · WINIFRED MASTERSON BURKE MED RES INST · PI GIBSON, GARY E · 1999 to 2020
$30.7M
Training in the Neurobiology of Aging and Alzheimers DiseaseT32AG000096 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI VIVEK SWARUP, Craig E Stark · 1985 to 2026
$9.6M
Pathogenic Impact of SUMO modification in Huntington's diseaseR01NS052789 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI THOMPSON, LESLIE MICHELS · 2006 to 2010
$1.9M
Neuroregulatory Mechanisms of PIAS1 and Implications for Huntington's DiseaseR01NS090390 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI DAVIDSON, BEVERLY L., THOMPSON, LESLIE MICHELS · 2015 to 2018
$1.8M
Huntingtin proline-rich region modulation of Huntington's disease pathogenesisR01NS077926 · NINDS · UNIVERSITY OF VIRGINIA · PI ZEITLIN, SCOTT · 2014 to 2018
$1.7M
Pathogenic impact of Huntington phosphorylation in Huntington's DiseaseR01NS072453 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI STEFFAN, JOAN SAWYER · 2012 to 2015
$1.3M
Neuroregulatory Mechanisms of PIAS1 and Implications for Huntington's DiseaseR56NS090390 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI THOMPSON, LESLIE MICHELS · 2014 to 2014
$565k
Pathogenic impact of Huntingtin phosphorylation in Huntington's DiseaseR56NS072453 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI STEFFAN, JOAN SAWYER · 2017 to 2017
$377k
NIA NIH HHS P01 AG014930NIA NIH HHS T32 AG000096NINDS NIH HHS R01 NS052789NINDS NIH HHS R01 NS072453NINDS NIH HHS R01 NS077926NINDS NIH HHS R01 NS090390NINDS NIH HHS R56 NS072453NINDS NIH HHS R56 NS090390
6 · The paper itself

Abstract

backgroundHuntington's disease (HD) is a progressive neurodegenerative disorder associated with aging, caused by an expanded polyglutamine (polyQ) repeat within the Huntingtin (HTT) protein. In HD, degeneration of the striatum and atrophy of the cortex are observed while cerebellum is less affected.

objectiveTo test the hypothesis that HTT protein levels decline with age, which together with HTT mutation could influence disease progression.

methodsUsing whole brain cell lysates, a unique method of SDS-PAGE and western analysis was used to quantitate HTT protein, which resolves as a monomer and as a high molecular weight species that is modulated by the presence of transglutaminase 2. HTT levels were measured in striatum, cortex and cerebellum in congenic homozygous Q140 and HdhQ150 knock-in mice and WT littermate controls.

resultsMutant HTT in both homozygous knock-in HD mouse models and WT HTT in control striatal and cortical tissues significantly declined in a progressive manner over time. Levels of mutant HTT in HD cerebellum remained high during aging.

conclusionsA general decline in mutant HTT levels in striatum and cortex is observed that may contribute to disease progression in homozygous knock-in HD mouse models through reduction of HTT function. In cerebellum, sustained levels of mutant HTT with aging may be protective to this tissue which is less overtly affected in HD.

Indexed as

Disease ProgressionAgingAnimalsCerebellumCerebral CortexCorpus StriatumDisease Models, AnimalFemaleGene Knock-In TechniquesHomozygoteHuntingtin ProteinHuntington DiseaseMaleMice, Inbred C57BLMutant ProteinsHtt protein, mouseHuntingtin ProteinMutant ProteinsAutophagyHuntingtinHuntington’s diseaseneurodegeneration

Identifiers

PMID29843246
PMCPMC6002862
OpenAlexW2804663373

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.