Rule learning, visuospatial function and motor performance in the Hdh(Q92) knock-in mouse model of Huntington's disease.
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.
Trueman
R C
RC
School of Biosciences, Cardiff University, Museum Avenue, Box 911, Cardiff CF10 3AX, Wales, UK. truemanrc@cardiff.ac.uk
Brooks
S P
SP
Jones
L
L
Dunnett
S B
SB
D000818:Animals; D002755:Choice Behavior; D003072:Cognition Disorders / Q000235:genetics / Q000503:physiopathology; D003216:Conditioning, Operant; D005260:Female; D055879:Gene Knock-In Techniques; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D011597:Psychomotor Performance; D011930:Reaction Time; D045442:Rotarod Performance Test; D055697:Taste Perception
C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins