Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Mismatch repair dissection by in vivo RNAi reveals dose-dependent modulators of somatic instability and proteome remodeling in Huntington's disease.

bioRxiv : the preprint server for biology·2026
Same author

WWOX contributes to DNA damage, but not somatic instability in Huntington's disease.

bioRxiv : the preprint server for biology·2026
Same author

Somatic CRISPR editing of <i>Msh3</i> mitigates Huntington's disease pathology in mice.

bioRxiv : the preprint server for biology·2026
Same author

Molecular features of a Huntington's disease knock-in minipig.

Disease models & mechanisms·2026
Same author

C57BL/6 BAC-CAG Huntington's disease mice show somatic CAG expansion and responses to small interfering RNAs comparable to the FVB strain.

bioRxiv : the preprint server for biology·2026
Same author

TRACE: Open-source software for quantifying somatic variation of tandem repeats by capillary electrophoresis.

Journal of Huntington's disease·2026

Related Experiment Video

Updated: Jan 1, 2026

A Robust Polymerase Chain Reaction-based Assay for Quantifying Cytosine-guanine-guanine Trinucleotide Repeats in Fragile X Mental Retardation-1 Gene
08:22

A Robust Polymerase Chain Reaction-based Assay for Quantifying Cytosine-guanine-guanine Trinucleotide Repeats in Fragile X Mental Retardation-1 Gene

Published on: September 16, 2019

8.3K

Assessing average somatic CAG repeat instability at the protein level.

Hubert Aviolat1, Ricardo Mouro Pinto2, Elizabeth Godschall1

  • 1Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Scientific Reports
|December 18, 2019
PubMed
Summary

This study quantifies mutant huntingtin (mHTT) using a novel protein-level assay that reflects CAG repeat instability. The method shows strong correlation with genomic DNA measurements in Huntington

More Related Videos

Author Spotlight: Characterizing DNA Replication of Pathogenic Repeats to Uncover Mechanisms of Replication Fork Stalling and Expansion
05:22

Author Spotlight: Characterizing DNA Replication of Pathogenic Repeats to Uncover Mechanisms of Replication Fork Stalling and Expansion

Published on: September 13, 2024

1.1K
Measuring RAN Peptide Toxicity in C. elegans
10:49

Measuring RAN Peptide Toxicity in C. elegans

Published on: April 30, 2020

7.0K

Related Experiment Videos

Last Updated: Jan 1, 2026

A Robust Polymerase Chain Reaction-based Assay for Quantifying Cytosine-guanine-guanine Trinucleotide Repeats in Fragile X Mental Retardation-1 Gene
08:22

A Robust Polymerase Chain Reaction-based Assay for Quantifying Cytosine-guanine-guanine Trinucleotide Repeats in Fragile X Mental Retardation-1 Gene

Published on: September 16, 2019

8.3K
Author Spotlight: Characterizing DNA Replication of Pathogenic Repeats to Uncover Mechanisms of Replication Fork Stalling and Expansion
05:22

Author Spotlight: Characterizing DNA Replication of Pathogenic Repeats to Uncover Mechanisms of Replication Fork Stalling and Expansion

Published on: September 13, 2024

1.1K
Measuring RAN Peptide Toxicity in C. elegans
10:49

Measuring RAN Peptide Toxicity in C. elegans

Published on: April 30, 2020

7.0K

Area of Science:

  • Neuroscience
  • Biochemistry
  • Genetics

Background:

  • Huntington's disease (HD) is characterized by expanded CAG repeats in the huntingtin (HTT) gene, leading to mutant huntingtin (mHTT) protein.
  • Quantifying mHTT protein, particularly its polyglutamine (polyQ) tract length, is crucial for understanding HD pathogenesis and developing therapeutics.

Purpose of the Study:

  • To develop and validate a novel protein-level assay for quantifying mutant huntingtin (mHTT) that reflects CAG repeat instability.
  • To establish a correlation between protein-level polyQ length measurements and genomic DNA CAG repeat lengths in HD models and human samples.

Main Methods:

  • Utilized Meso Scale Discovery (MSD) assay with MW1 antibody targeting the polyglutamine (polyQ) tract of mHTT.
  • Assessed polyQ length-dependent effects on MSD signals using purified mHTT exon1 proteins and endogenous full-length mHTT from HD knock-in (KI) mouse brains.
  • Correlated protein-level average polyQ length quantification with genomic DNA CAG repeat length determined by PCR.

Main Results:

  • The MSD assay signal with MW1 antibody demonstrated a strong correlation with polyQ length, showing increased signal with as little as 7 additional glutamine residues.
  • Similar polyQ length-dependent effects were observed for endogenous full-length mHTT in HD KI mouse brains.
  • The developed protein-level assay showed a strong correlation with genomic DNA CAG repeat lengths in both HdhQ140 KI mouse striatal tissue and human HD postmortem cortex.

Conclusions:

  • A novel protein-level assay effectively quantifies mutant huntingtin (mHTT) and reflects CAG repeat instability.
  • This method provides a reliable way to assess average polyQ length at the protein level, correlating strongly with genomic CAG repeat length.
  • CAG repeat instability in mutant huntingtin is demonstrably reflected at the protein level, offering a valuable tool for HD research.