Evidence map›Paper›PMID 30452420›Full record

ArticleJournal of Huntington's disease2018

Longitudinal Biochemical Assay Analysis of Mutant Huntingtin Exon 1 Protein in R6/2 Mice.

Eva L Morozko, Joseph Ochaba, Sarah J Hernandez, Alice Lau, Isabella Sanchez, Iliana Orellana, Lexi Kopan, Joshua Crapser, Janet H Duong, Julia Overman and 4 more

Open access · hybridAbstract 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 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.4field-weighted citation impact, top 43% 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

5 citing papers in PubMed, 6 citations in OpenAlex.

  1. Treatment of Huntington's disease with a pan-HTT-targeting CRISPR nuclease.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  2. Article
  3. Article
  4. Article
  5. 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
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

14 authors at 1 institution in 1 country.

Eva L MorozkoUniversity of California, Irvine, Neurobiology and Behavior, Irvine, CA, USA.
Joseph OchabaUniversity of California, Irvine, Neurobiology and Behavior, Irvine, CA, USA.
Sarah J HernandezUniversity of California, Irvine, Neurobiology and Behavior, Irvine, CA, USA.
Alice LauUniversity of California, Irvine, Psychiatry & Human Behavior, Irvine, CA, USA.
Isabella SanchezUniversity of California, Irvine, Neurobiology and Behavior, Irvine, CA, USA.
Iliana OrellanaInstitute for Memory Impairment and Neurological Disorders, University of California, Irvine, CA, USA.
Lexi KopanUniversity of California, Irvine, Neurobiology and Behavior, Irvine, CA, USA.
Joshua CrapserUniversity of California, Irvine, Neurobiology and Behavior, Irvine, CA, USA.
Janet H DuongUniversity of California, Irvine, Neurobiology and Behavior, Irvine, CA, USA.
Julia OvermanUniversity of California, Irvine, Neurobiology and Behavior, Irvine, CA, USA.
Silvia YeungInstitute for Memory Impairment and Neurological Disorders, University of California, Irvine, CA, USA.
Joan S SteffanUniversity of California, Irvine, Psychiatry & Human Behavior, Irvine, CA, USA.
Jack ReidlingInstitute for Memory Impairment and Neurological Disorders, University of California, Irvine, CA, USA.
Leslie M ThompsonUniversity of California, Irvine, Neurobiology and Behavior, Irvine, CA, USA.
University of California, Irvine · US

Funding

Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Melanie Funes · 1994 to 2026
$57.9M
University of California Health Participation in the National COVID Cohort Collaborative (N3C)UL1TR001414 · NCATS · UNIVERSITY OF CALIFORNIA-IRVINE · PI COOPER, DAN M, VILAIN, ERIC J. · 2015 to 2023
$35.1M
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
NRSA Training CoreTL1TR001415 · NCATS · UNIVERSITY OF CALIFORNIA-IRVINE · PI CAIOZZO, VINCENT JAMES, HEAD, ELIZABETH · 2015 to 2023
$4.2M
Training Program in Stem Cell Translational Medicine for Neurological DisordersT32NS082174 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI PETER John DONOVAN, Leslie Michels Thompson · 2013 to 2026
$3.3M
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
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
Investigation of ApiCCT1 for Huntingtons disease therapeuticsF31NS087923 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI OVERMAN, JULIA KRISTINE JANAE · 2014 to 2016
$100k
NCATS NIH HHS TL1 TR001415NCATS NIH HHS UL1 TR001414NCI NIH HHS P30 CA062203NIA NIH HHS T32 AG000096NINDS NIH HHS F31 NS087923NINDS NIH HHS R01 NS052789NINDS NIH HHS R01 NS072453NINDS NIH HHS R01 NS090390NINDS NIH HHS R56 NS072453NINDS NIH HHS R56 NS090390NINDS NIH HHS T32 NS082174
6 · The paper itself

Abstract

backgroundBiochemical analysis of mutant huntingtin (mHTT) aggregation species in HD mice is a common measure to track disease. A longitudinal and systematic study of how tissue processing affects detection of conformers has not yet been reported. Understanding the homeostatic flux of mHTT over time and under different processing conditions would aid in interpretation of pre-clinical assessments of disease interventions.

objectiveProvide a systematic evaluation of tissue lysis methods and molecular and biochemical assays in parallel with behavioral readouts in R6/2 mice to establish a baseline for HTT exon1 protein accumulation.

methodsEstablished biochemical methods were used to process tissue from R6/2 mice of specific ages following behavior tasks. Aggregation states and accumulation of mHTT exon 1 protein were evaluated using multiple break and assay methods to determine potential conformational flux assay specificity in detection of mHTT species, and tissue specificity of conformers.

resultsDetection of mHTT exon 1 protein species varied based on biochemical processing and analysis providing a baseline for subsequent studies in R6/2 mice. Insoluble, high molecular weight species of mHTT exon 1 protein increased and tracked with onset of behavioral impairments in R6/2 mice using multiple assay methods.

conclusionsConformational flux from soluble monomer to high molecular weight, insoluble species of mHTT exon 1 protein was generally consistent for multiple assay methods throughout R6/2 disease progression; however, the results support the use of multiple biochemical techniques to detect mHTT exon 1 protein species for preclinical assessments in HD mouse models expressing mHTT exon 1 protein.

Indexed as

AnimalsBrainDisease Models, AnimalElectrophoresis, Agar GelElectrophoresis, Polyacrylamide GelExonsHumansHuntingtin ProteinHuntington DiseaseLongitudinal StudiesMiceMice, Inbred StrainsMice, TransgenicProtein Aggregation, PathologicalSpecimen HandlingHTT protein, humanHuntingtin ProteinaggregationconformerHuntingtinHuntington’s diseaseprotein aggregatesprotein homeostasis

Identifiers

PMID30452420
PMCPMC6294605
OpenAlexW2901951196

What OpenQuestion holds

Textmetadata
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.