Mouse Genome Informatics
cx
    Sncatm1Nbm/Sncatm1Nbm
Tg(SNCA*A53T)1Nbm/Tg(SNCA*A53T)1Nbm
Tg(SNCA*A53T)2Nbm/Tg(SNCA*A53T)2Nbm

involves: 129S6/SvEvTac * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
growth/size/body
N
• body weigh does not differ from controls measured out to 18 months of age (J:156741)

behavior/neurological
• 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
• total distance traveled in the open field apparatus is reduced compared to controls at 6 months and remains abnormal at 18 months
• 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

nervous system
N
• 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 (J:156741)
• striatal tissue dopamine and dopamine metabolite content are not different from controls at 11 and 18 months (J:156741)
• no progressive loss of dopaminergic neurons in the substantia nigra, pars compacta (SNpc) is observed (J:156741)
• olfaction and cardiac innervation by the autonomic nervous system are not affected by the transgenes (J:156741)
• some dystrophic synapses are observed in rare instances at 12 or 22 months
• protein is present in tyrosine hydroxylase (TH)-immunoreactive neuronal cell bodies within myenteric and submucosal plexuses; varicose TH-positive terminals of noradrenergic sympathetic neurons
• most alpha-synuclein positive neurons, especially in the myenteric plexus are not coincident with TH immunostaining
• 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

digestive/alimentary system
• 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
• 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)
• 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
• this phenotype is present at 3 months and persists through 18 months of age
• 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

cardiovascular system
N
• no defects in autonomic cardiac innervation are detected (J:156741)

taste/olfaction
N
• mice show no impairments in olfaction at 12 and 18 months of age (J:156741)
• olfactory bulbs show no degeneration or protein aggregation at 12 and 18 months of age (J:156741)

Mouse Models of Human Disease
OMIM IDRef(s)
Parkinson Disease 1, Autosomal Dominant; PARK1 168601 J:156741