Neurobehavioral Anomalies in the Pitx3/ak Murine Model of Parkinson's Disease and MPTP.

Pitx3/ak null mutants are characterized by basal ganglia pathology in a manner resembling Parkinson's disease (PD), with decline in substantia nigra cell numbers as well as striatal tyrosine hydroxylase expression. Although young adult Pitx3/ak mutants were deficient in motor coordination tests, they were more active than non-transgenic controls in the open-field, unlike PD-related bradykinesia. On the SHIRPA primary screen, the mutants displayed body tremor, hyperactivity in the viewing jar, anomalies in eye morphology as well as a higher degree of hindlimb clasping and myoclonic jumping. Increased hindlimb clasping time and rotorod deficits seen in mutants were also exhibited by mice injected with MPTP, indicating an influence of dopamine on these behaviors.