Behavioral phenotypes and pharmacology in genetic mouse models of Parkinsonism

Abstract

Prior to the discovery of genes associated with familial forms of Parkinson's disease, animal models of Parkinson's disease mainly consisted of toxin models based exclusively on the degeneration of nigrostriatal dopamine neurons. These traditional models have provided valuable insight into symptomatic treatments for Parkinson's disease; however, they lack the broad extra-nigral pathology and the progression that is observed in the disease. The novel genetic mouse models recently generated are advantageous because they have mutations that are known to cause familial Parkinson's disease and thus they have good construct validity. To maximize the utility of these models, a thoughtful phenotypical characterization is important. Our laboratory has assembled a battery of behavioral tests to assess sensorimotor function in genetic mouse models of Parkinsonism. This review discusses the sensitivity of these tests in different genetic mice in addition to their behavioral response to dopamine agonists.