Motor, emotional and cognitive deficits in adult BACHD mice: a model for Huntington's disease

Behav Brain Res. 2013 Feb 1;238:243-51. doi: 10.1016/j.bbr.2012.10.039. Epub 2012 Oct 30.


Rationale: Huntington's disease (HD) is characterized by progressive motor dysfunction, emotional disturbances and cognitive deficits. It is a genetic disease caused by an elongation of the polyglutamine repeats in the huntingtin gene. Whereas HD is a complex disorder, previous studies in mice models have largely been confined to assessing motor deficits.

Objectives: The aim of the present studies is a comprehensive phenotypical assessment of not only motor and gait deficits, but also of emotional and cognitive deficits in adult BACHD mice.

Material and methods: 46 male BACHD mice between 9 and 10 months of age were used. Wild type (+/+) and transgenic (+/T) mice were tested for motor deficits on a Rotarod and Catwalk system. Emotional deficits were assessed with the zero-maze and fear conditioning tests. Cognitive deficits in a strategy shifting task were evaluated in a cross-maze test.

Results: Comparing +/T and +/+ mice, we replicated the motor deficits in the transgenic mice that were previously described in the Rotarod test. For the first time, motor coordination imbalances in +/T animals are described in the Catwalk gait analysis system. +/T mice showed more anxiety-like behavior in the zero-maze test and a higher freezing response in the fear conditioning test. Reversal and strategy shifting impairments were demonstrated in the cross-maze, indicative of a disturbed prefrontal-striatal pathway.

Conclusion: The results suggest that BACHD mice represent an animal model with a high degree of face validity for HD and may be very useful for testing novel therapeutic strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / genetics
  • Anxiety / physiopathology
  • Behavior, Animal / physiology
  • Cognition Disorders / genetics
  • Cognition Disorders / physiopathology*
  • Conditioning, Psychological / physiology
  • Disease Models, Animal
  • Emotions / physiology*
  • Fear / physiology
  • Gait / physiology
  • Huntington Disease / genetics
  • Huntington Disease / physiopathology*
  • Maze Learning / physiology*
  • Mice
  • Mice, Transgenic
  • Motor Activity / genetics
  • Motor Activity / physiology*
  • Motor Skills / physiology*
  • Rotarod Performance Test