Mouse Genome Informatics
cx1
    Sncatm1Rosl/Sncatm1Rosl
Tg(Prnp-SNCA*A53T)83Vle/Tg(Prnp-SNCA*A53T)83Vle

involves: 129X1/SvJ * C3H * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• following injection of LPS into the substantia nigra
• following injection of LPS into the substantia nigra, mice exhibit an increased loss of dopaminergic neurons that is associated with insoluble and aggregated SNCA compared to in Sncatm1Rosl Tg(Prnp-SNCA)7Vle and Sncatm1Rosl homozygotes
• however, loss of dopamine neurons is not due to an abnormal inflammatory response following injection of LPS into the substantia nigra

immune system
• following injection of LPS into the substantia nigra, mice exhibit an increased loss of dopaminergic neurons compared to in Sncatm1Rosl Tg(Prnp-SNCA)7Vle and Sncatm1Rosl homozygotes


Mouse Genome Informatics
tg2
    Tg(Prnp-SNCA*A53T)83Vle/Tg(Prnp-SNCA*A53T)83Vle
involves: C3H * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

growth/size
• by 8 months of age, begin to lose weight

behavior/neurological
• over time become unable to feed themselves
• by 8 months of age, grooming is neglected
• unable to right themselves when placed on their sides
• temulous motion is seen in some mice, possibly related to attempted muscular activity
• eventually are unable to stand up and support their own body weight
• develop hunched backs by 8 months of age
• by 8 months of age, exhibit severe movement impairment with resistance to passive movement and partial paralysis of limbs, accompanied by periods of freezing of hindlimb
• reduced ambulation by 8 months of age
• partial paralysis of limbs is observed by 8 months of age, beginning at a hindleg but affecting all limbs within a few days

nervous system
• astrocytic gliosis
• endoneurial space is increased and axons are filled with vacuoles in the ventral roots of aged mice
• develop age-dependent intracytoplasmic neuronal alpha-synuclein inclusions that contain 10-16 nm wide fibrils similar to those seen in human alpha-synucleinopathies, with dense accumulation in the spinal cord, brainstem, cerebellum, and thalamus
• following axonal degeneration, the myelin sheath loosens and unravels
• show signs of neurodegeneration by 8 months of age and develop neurodegenerative disease within 16 months of age
• significant axonal degeneration in aged mice

muscle
• exhibit sparse neurogenic muscle atrophy

Mouse Models of Human Disease
OMIM IDRef(s)
Parkinson Disease 1, Autosomal Dominant; PARK1 168601 J:76657


Mouse Genome Informatics
tg3
    Tg(Prnp-SNCA*A53T)83Vle/0
involves: C3H * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• develop the severe and complex motor impairment leading to paralysis and death that is seen in homozygous transgenics, however onset is delayed from 16 months of age to 22-28 months of age

nervous system
• develop a similar neurodegenerative disease that is observed in homozygous transgenic mice, however onset is delayed from 16 months of age to 22-28 months of age

Mouse Models of Human Disease
OMIM IDRef(s)
Parkinson Disease 1, Autosomal Dominant; PARK1 168601 J:76657