The AS/AGU rat provides an alternative to experimentally produced laboratory models of basal ganglia
disorders. This mutant is characterised by disturbances of movement including clumsy gait, whole body
tremor, rigidity and difficulty in initiating movement. From an early age, there is a profound depletion of
extracellular dopamine in the dorsal caudate-putamen as measured via in vivo microdialysis; levels are only
10–20% of those found in the parent Albino Swiss (AS) strain. Subsequently a depletion of whole tissue
dopamine levels occurs and, later still, loss of dopaminergic cells in the substantia nigra pars compacta. The
dysfunction in movement and the nigrostriatal dopaminergic system are clearly linked, since movement can
be ameliorated by L-DOPA administration. Furthermore, there are depletions in glucose utilisation in several
regions of the basal ganglia circuitry, including the substantia nigra pars compacta, the subthalamic nucleus
and the ventrolateral thalamus. The AS/AGU rat represents a unique opportunity to investigate the
intrinsic factors controlling the integrity of dopaminergic systems and the recent successful positional cloning
of the agu gene will allow the molecular mechanisms underlying this interesting phenotype to be analysed.