mammalian phenotype

• nervous system phenotype
  • Normal - dorsal motor nucleus of the vagus shows no abnormal alpha-synuclein aggregation and any widespread aggregates are not detected in brain homogenates of 5 and 18 month-old animals
  (MGI Ref ID J:156741)
  • Normal - olfaction and cardiac innervation by the autonomic nervous system are not affected by the transgenes
  (MGI Ref ID J:156741)
  • Normal - striatal tissue dopamine and dopamine metabolite content are not different from controls at 11 and 18 months
  (MGI Ref ID J:156741)
  • Normal - no progressive loss of dopaminergic neurons in the substantia nigra, pars compacta (SNpc) is observed
  (MGI Ref ID J:156741)

• cardiovascular system phenotype
  • Normal - no defects in autonomic cardiac innervation are detected
  (MGI Ref ID J:156741)

• taste/olfaction phenotype
  • Normal - mice show no impairments in olfaction at 12 and 18 months of age
  (MGI Ref ID J:156741)
  • Normal - olfactory bulbs show no degeneration or protein aggregation at 12 and 18 months of age
  (MGI Ref ID J:156741)

• growth/size/body region phenotype
  • Normal - body weigh does not differ from controls measured out to 18 months of age
  (MGI Ref ID J:156741)

nervous system phenotype

• alpha-synuclein inclusion body
  • most alpha-synuclein positive neurons, especially in the myenteric plexus are not coincident with TH immunostaining
  (MGI Ref ID J:156741)
  • proteinase K-resistant alpha-synuclein aggregates are observed in the nuclear and perinuclear cytoplasm of enteric nervous system neurons in mice showing gastrointestinal motility dysfunction
  (MGI Ref ID J:156741)
  • protein is present in tyrosine hydroxylase (TH)-immunoreactive neuronal cell bodies within myenteric and submucosal plexuses; varicose TH-positive terminals of noradrenergic sympathetic neurons
  (MGI Ref ID J:156741)

• abnormal hippocampus morphology
  • some dystrophic synapses are observed in rare instances at 12 or 22 months
  (MGI Ref ID J:156741)

behavior/neurological phenotype

• impaired coordination
  • males and females exhibit consistently reduced latency to fall beginning at 6 months; this persisted at 1 year of age and more pronounced at 18 months; endurance and coordination in the rotating rod test are abnormal
  (MGI Ref ID J:156741)

• hypoactivity
  • distance traveled decreases with age, showing reduced ambulatory distance traveled compared to controls at 12 and 18 months; reduction is generalized, not specific to a particular type of movement or region
  (MGI Ref ID J:156741)
  • total distance traveled in the open field apparatus is reduced compared to controls at 6 months and remains abnormal at 18 months
  (MGI Ref ID J:156741)

digestive/alimentary phenotype

• abnormal digestive system physiology
  • proteinase K-resistant alpha-synuclein aggregates are observed in the nuclear and perinuclear cytoplasm of enteric nervous system neurons in mice showing gastrointestinal motility dysfunction
  (MGI Ref ID J:156741)

• abnormal intestinal transit time
  • stal colonic motility)
  (MGI Ref ID J:156741)
  • whole-gut transit time (WGTT) is prolonged compared to controls starting at 3 months and is markedly prolonged at 6 months persisting through 18 months of age; this phenotype does not differ between males and females in contrast to bead expulsion time (distal colonic motility)
  (MGI Ref ID J:156741)

• abnormal large intestinal transit time
  • motility of distal colon is reduced compared to controls with males showing around a 4-5 fold prolongation in expulsion compared to controls; reduction is exaggerated compared to females
  (MGI Ref ID J:156741)
  • amount of stool passed/unit time and stool water content are unchanged at 3 months of age but by 6 months these parameters are reduced to comparable degrees
  (MGI Ref ID J:156741)
  • this phenotype is present at 3 months and persists through 18 months of age
  (MGI Ref ID J:156741)