Behavioral assessment of genetic mouse models of Huntington's disease

Abstract

Huntington's disease (HD) is a monogenetic, neurodegenerative disease. It is fatal, and although treatments are available for minor symptomatic relief, it remains incurable. Careful study of models of HD remains critical for elucidation of disease mechanisms and for the development of therapeutics. Models that rapidly develop to end stage are useful to assess efficacy of therapeutics for neuroprotection in relatively short experiments. However, the striatum, an area of brain traditionally associated with degeneration in HD already shows extensive atrophy by the time the symptoms manifest in patients, indicating that substantial degeneration occurs in the years preceding clinical onset. Thus, it is vital to also study models that allow analysis of the early pre-manifest disease stage. This requires the development of sensitive output measures to reveal deficits before the onset of obvious anomalies. Here, we briefly review the characteristics of -several mouse models of HD and outline methods for analysis of behavioral deficits in both severe fast - progressing models and for early stages of disease in slowly progressive models. © 2011 Springer Science+Business Media, LLC.