behavior/neurological phenotype

• impaired coordination
  • Normal - however, no differences in the latency to fall in the inverted screen test is seen
  (MGI Ref ID J:201991)
  • 18 month old mutants show a reduced latency to fall on the rotarod test and are impaired on the multiple static rods test
  (MGI Ref ID J:201991)

• short stride length
  • reduction in forepaw stride length in 18 month old mutants
  (MGI Ref ID J:201991)

digestive/alimentary phenotype

• constipation
  • dry stool weight is increased in males but not females, independent of age; however, stool frequency and stool water content are normal, indicating constipation-like phenotype
  (MGI Ref ID J:201991)

homeostasis/metabolism phenotype

• increased dopamine level
  • net dopamine content is unchanged in caudate putamen or nucleus accumbens at 3-4 and 12 months of age, however at 18 months of age, dopamine content is greater in the caudate putamen
  (MGI Ref ID J:201991)

nervous system phenotype

• abnormal dopaminergic neuron morphology
  • vesicles in dopamine axons of the dorsal striatum are more clustered than in controls at 3 months of age; the frequency distribution of intervesicle distance is reduced and vesicles are 3 times less dispersed
  (MGI Ref ID J:201991)

• abnormal neuron physiology
  • substantia nigra pars compacta dopamine neurons exhibit age-dependent reductions (almost 30%) in firing rates in vivo
  (MGI Ref ID J:201991)

• abnormal synaptic dopamine release
  • greatest deficits in dopamine release are seen in the dorsal and lateral striatum
  (MGI Ref ID J:201991)
  • efore the loss of dopamine neurons and persists throughout their lifespan
  (MGI Ref ID J:201991)
  • the dopamine release deficit persists in the presence of nicotinic receptor blockade by dihydro-beta-erythroidine
  (MGI Ref ID J:201991)
  • Normal - dopamine uptake kinetics are normal and norepinephrine and 5-hydroxytryptamine axonal release are normal
  (MGI Ref ID J:201991)
  • in the dorsal striatum, mean peak extracellular concentrations of dopamine evoked by single electrical pulses across distributed recording sites are on average about 30% lower than in controls; this reduced release is seen from a young age of 3-4 months before the loss of dopamine neurons and persists throughout their lifespan
  (MGI Ref ID J:201991)

• neuron degeneration
  • 18 month old mutants exhibit loss of substantia nigra pars compacta dopamine neurons
  (MGI Ref ID J:201991)
  • Normal - however, aggregation of alpha-synuclein is not seen in the substantia nigra pars compacta or striatum
  (MGI Ref ID J:201991)

• loss of dopaminergic neurons
  • 18 month old mutants exhibit loss of substantia nigra pars compacta dopamine neurons
  (MGI Ref ID J:201991)