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Related Concept Videos

Huntington Disease l: Introduction01:21

Huntington Disease l: Introduction

Huntington disease or HD is a progressive, fatal neurodegenerative disorder inherited in an autosomal dominant pattern.PathophysiologyIt is caused by expansion of the CAG trinucleotide repeat in the HTT gene on chromosome 4 (4p16.3), producing an abnormal huntingtin protein with an expanded polyglutamine tract. This misfolded protein disrupts cellular function, leading to neuronal death. Normal alleles have ≤26 repeats, 27–35 are intermediate (risk of expansion), 36–39 show reduced penetrance,...
Lethal Alleles02:41

Lethal Alleles

Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...

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Related Experiment Video

Updated: Jun 27, 2026

A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging
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CAG repeat lengths > or =335 attenuate the phenotype in the R6/2 Huntington's disease transgenic mouse.

I Dragatsis1, D Goldowitz, N Del Mar

  • 1Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.

Neurobiology of Disease
|November 26, 2008
PubMed
Summary

Longer CAG repeats in Huntington's disease models unexpectedly increased lifespan. Extreme repeat lengths may reduce mutant protein levels and nuclear entry, potentially attenuating disease severity.

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Last Updated: Jun 27, 2026

A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging
09:37

A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging

Published on: July 14, 2016

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05:48

Removal of an Internal Translational Start Site from mRNA While Retaining Expression of the Full-Length Protein

Published on: March 16, 2022

Area of Science:

  • Neuroscience
  • Genetics
  • Molecular Biology

Background:

  • Huntington's disease (HD) is a neurodegenerative disorder caused by expanded CAG repeats in the huntingtin gene.
  • The R6/2 mouse model exhibits HD-like pathology with shorter CAG repeats.

Purpose of the Study:

  • To investigate the impact of extreme CAG repeat expansions on HD pathogenesis in the R6/2 mouse model.
  • To determine if increased polyglutamine (polyQ) length correlates with disease severity or lifespan.

Main Methods:

  • Spontaneous elongation of CAG repeats in R6/2 mice to >=335 repeats.
  • Analysis of protein aggregation, transgene expression levels, and neurological/neurochemical abnormalities.
  • Comparison of lifespan and phenotype between mice with 150 and >=335 CAG repeats.

Main Results:

  • Mice with >=335 CAG repeats showed significantly increased lifespan (>20 weeks) compared to those with 150 repeats (12 weeks).
  • Extreme repeats led to large aggregates in neuronal cytoplasm but infrequent intranuclear aggregates.
  • Transgene message and protein levels were reduced by one-third in >=335 CAG mice.
  • Neurological deficits were delayed and less severe in mice with extreme CAG repeats.

Conclusions:

  • Polyglutamine length and Huntington's disease pathogenicity may not be linearly related.
  • Extreme CAG repeat expansions can attenuate disease phenotype, potentially due to reduced mutant protein levels and limited nuclear entry.