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Pathogenic mechanisms
A29 Frontostriatal pathology in the (C57BL/6J) YAC128 mouse uncovered by the operant delayed alternation task
  1. S Brooks1,
  2. L Jones2,
  3. S B Dunnett1
  1. 1Brain Repair Group, School of Biosciences, Cardiff University, Cardiff, Wales, UK
  2. 2Department of Psychological Medicine, Wales School of Medicine, Cardiff University, Cardiff, Wales, UK

Abstract

Background To determine the suitability of a mouse line for the trailing of therapeutic interventions, it is necessary to identify behavioural abnormalities that reflect disease relevant pathology. In Huntington's disease (HD), several mouse lines have been developed that attempt to recapitulate the disease. The YAC128 mouse on a FVB background exhibits numerous behavioural abnormalities, including cognitive and motor deficits. A C57BL/6J variant of this mouse line has been created that is free from the retinal degeneration of the FVB line, but relatively little work has been conducted on this line.

Aims The aim of the present study was to probe the C57BL/6J YAC128 mouse line for HD relevant cognitive deficits using the operant delayed alternation task, a task highly sensitive to frontostriatal dysfunction.

Methods YAC128 mice were tested at 8 and 22 months of age. The delayed alternation task was run in operant nine hole box chambers. The task requires that the mouse develops an alternating response pattern to gain sweet rewards. Task performance is measured by response accuracy and reaction times to make a correct response.

Results At 8 months of age, performance of the YAC128 mice was impaired on accuracy of response and reaction time measures. By 22 months of age, the same impairments were present but more severe.

Conclusions The YAC128 mouse demonstrates severe dysfunction of the frontostraital circuits of the brain. The deficit is present at 7 months of age and more severe at 22 months of age. This deficit closely resembles the deficits found in HD and as such suggests the YAC128 (C57BL/6J) mouse may be a useful model on which to test novel therapeutic strategies.

  • mouse
  • YAC128
  • cognitive
  • delayed alternation
  • operant
  • behaviour

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