Rule learning, visuospatial function and motor performance in the Hdh(Q92) knock-in mouse model of Huntington's disease

Behav Brain Res. 2009 Nov 5;203(2):215-22. doi: 10.1016/j.bbr.2009.05.006. Epub 2009 May 13.

Abstract

Among a range of genetic mouse models of Huntington's disease, knock-in models that express full-length mutant huntingtin tend to have a slower developing and less severe behavioural phenotype than transgenic models carrying truncated variations of the human gene; as a result, these more subtle full-length knock-in models have been relatively neglected for behavioural and therapeutic studies. In the current study, we show that full-length knock-in Hdh(Q92) mice exhibit marked impairments at a relatively young age in delayed alternation, a cognitive test conducted in 9-hole operant chambers classically associated with prefrontal and corticostriatal function. Additional tests of motivation, visuomotor and rotarod performance were undertaken to determine the frontal-like specificity of the impairment; aspects of sensorimotor and motivational as well as cognitive performance were deficient in Hdh(Q92/Q92) mice in comparison with their wildtype littermates by 27 months of age. The present results demonstrate that Hdh(Q92/Q92) mice do exhibit clear impairments on a range of sensory, motor, motivational and cognitive tests, provided appropriate sensitive tasks are used.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Choice Behavior
  • Cognition Disorders / genetics
  • Cognition Disorders / physiopathology
  • Conditioning, Operant
  • Female
  • Gene Knock-In Techniques
  • Huntingtin Protein
  • Huntington Disease / genetics
  • Huntington Disease / physiopathology*
  • Male
  • Mice
  • Mice, Transgenic
  • Motor Activity
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Psychomotor Performance
  • Reaction Time
  • Rotarod Performance Test
  • Taste Perception

Substances

  • Htt protein, mouse
  • Huntingtin Protein
  • Nerve Tissue Proteins
  • Nuclear Proteins