title: Motor, emotional and cognitive deficits in adult BACHD mice: a model for Huntington's disease.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: EVOTEC AG, Essener Bogen 7, 22419 Hamburg, Germany. yah-se.abada@evotec.com
authors.forename: Yah-se K
authors.initials: YS
authors.lastname: Abada
authors.forename: Rudy
authors.initials: R
authors.lastname: Schreiber
authors.forename: Bart
authors.initials: B
authors.lastname: Ellenbroek
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000503:physiopathology; D001522:Behavior, Animal / Q000502:physiology; D003072:Cognition Disorders / Q000235:genetics / Q000503:physiopathology*; D003213:Conditioning, Psychological / Q000502:physiology; D004195:Disease Models, Animal; D004644:Emotions / Q000502:physiology*; D005239:Fear / Q000502:physiology; D005684:Gait / Q000502:physiology; D006816:Huntington Disease / Q000235:genetics / Q000503:physiopathology*; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics / Q000502:physiology*; D009048:Motor Skills / Q000502:physiology*; D045442:Rotarod Performance Test