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C04 A Longitudinal Behavioural Characterisation of the HDHQ111 Mouse Model of Huntington’s Disease
  1. E Yhnell,
  2. SB Dunnett,
  3. SP Brooks
  1. The Brain Repair Group, Cardiff University, Cardiff, UK

Abstract

Background Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease caused by an expansion of a CAG polyglutamine repeat within the first exon of the huntingtingene. A range of mouse models are currently available for modelling HD, however these models must be characterised to determine their reliability in recapitulating HD symptoms. Knock-in mouse models have been previously shown to demonstrate subtle early cognitive phenotypes, followed by the appearance of motor disturbances which accurately reflect the symptom development of the human disease.

Aims We sought to characterise the development of both motor and cognitive symptoms in HdhQ111 heterozygous mice to determine whether they recapitulate the core symptoms of the human disease.

Methods The motor phenotype was investigated very three months using a battery of motor tests including; rotarod, balance beam, grip strength, locomotor activity and gait analysis. The cognitive phenotype was explored every six months utilising 9-hole operant boxes and an operant battery of tasks which included; fixed ratio, progressive ratio and the 5-choice serial reaction time task (5CSRTT).

Results No significant differences were demonstrated in the fixed or progressive ratio tasks. However, HdhQ111 heterozygous animals were significantly impaired in the 5CSRTT at 6 and 12 months of age. Significant motor problems were observed in HdhQ111 heterozygous animals on the accelerating rotarod from 12 months of age. Balance beam results indicated motor deficits beginning at 9 months of age and additional problems with co-ordination from 12 months of age. No significant differences were observed in grip strength, general locomotor activity or gait analysis.

Conclusions Deficits in the 5CSRTT, followed by motor problems which occur later in the disease accurately reflect the human condition and make the HdhQ111 mouse model an ideal model for testing novel therapeutics.

Keywords
  • Behaviour
  • longitudinal
  • mouse model
  • motor
  • cognitive

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