Correlations Between Mutant Huntingtin Aggregates and Behavioral Changes in R6/1 Mice

J Huntingtons Dis. 2020;9(1):33-45. doi: 10.3233/JHD-190352.


Background: Huntington's disease (HD) is a neurodegenerative disorder caused by the expansion of the trinucleotide CAG in the HD gene. While the presence of nuclear aggregates of mutant huntingtin (mHtt) in neurons is a hallmark of HD, the reason behind its toxicity remains elusive.

Objective: The present study was conducted to assess a correlation between the number of mHtt aggregates and the severity of HD symptoms in R6/1 mice.

Methods: We investigated correlations between behavioral deficits and the level of nuclear mHtt aggregates in different neuroanatomical regions in 3-month-old R6/1 mice, the age at which a large variability of symptom severity between animals has been observed.

Results: R6/1 mice were deficient in instinctive and anxiety related behaviors as well as long-term memory capabilities. Significant differences were also found between the sexes; female transgenic mice displayed less severe deficits than males. While the level of mHtt aggregates was correlated with the severity of HD phenotypes in most regions of interest, an opposite relationship also was found for some other regions examined.

Conclusions: The obtained results suggest harmful and region-specific roles of mHtt aggregates in HD symptoms.

Keywords: Mutant huntingtin aggregates; R6/1 mice; anxiety; instinctive behavior; motor activity; short-term and long-term memory; spatial memory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / physiology*
  • Disease Models, Animal
  • Female
  • Gray Matter / metabolism*
  • Huntingtin Protein / metabolism*
  • Huntington Disease / metabolism*
  • Huntington Disease / physiopathology*
  • Male
  • Mice
  • Mice, Transgenic
  • Mutant Proteins / metabolism*
  • Protein Aggregates*
  • Severity of Illness Index


  • Htt protein, mouse
  • Huntingtin Protein
  • Mutant Proteins
  • Protein Aggregates