Mouse Genome Informatics
cx1
    Atp13a2tm1.2Wtd/Atp13a2tm1.2Wtd
Tg(Prnp-SNCA*A53T)83Vle/0

involves: 129 * C3H * C57BL/6
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
cellular
• mice show a similar level of lysosomal accumulation as seen in single Atp13a2 homozygotes at 3 and 9 months of age

nervous system
• mice show similar levels of gliosis at 3 months of age and decreased levels of gliosis at 9 months compared to single Atp13a2 homozygotes


Mouse Genome Informatics
cx2
    Sncatm1Rosl/Sncatm1Rosl
Tg(Prnp-SNCA*A53T)83Vle/Tg(Prnp-SNCA*A53T)83Vle

involves: 129X1/SvJ * C3H * C57BL/6
Key:
phenotype observed in females
phenotype observed in males
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
tg3
    Tg(Prnp-SNCA*A53T)83Vle/Tg(Prnp-SNCA*A53T)83Vle
involves: C3H * C57BL/6
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging

growth/size/body
• 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
• show signs of neurodegeneration by 8 months of age and develop neurodegenerative disease within 16 months of age
• significant axonal degeneration in aged mice
• following axonal degeneration, the myelin sheath loosens and unravels

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
tg4
    Tg(Prnp-SNCA*A53T)83Vle/0
involves: C3H * C57BL/6
Key:
phenotype observed in females
phenotype observed in males
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 (J:76657)

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 (J:76657)
• mice develop some inclusions that are composed of both tau and alpha-synuclein (J:127923)
• about 25% of diseased mutants accumulate abundant tau-positive threads, grains and spheroids in regions of the pons, midbrain, and spinal core
• rare perikaryal tau inclusions with morphology of a pre-tangle are seen
• less frequent tau inclusions are present in another 25% of symptomatic mutants but none are seen in the rest 50% of diseased mutants
• mice exhibit formation of abundant alpha-synuclein inclusions

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


Mouse Genome Informatics
tg5
    Tg(Prnp-SNCA*A53T)83Vle/?
B6;C3-Tg(Prnp-SNCA*A53T)83Vle/J
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• 6 and 10 month, but not 3 month, old mice do not sniff novel scent more than familiar scent

homeostasis/metabolism
• decrease in acetylcholinesterase activity in olfactory bulb in 6 and 10 month old mice

nervous system
• increase in dopaminergic neurons in olfactory bulb glomerular layer in 10 month old mice
• decreased numbers of cholinergic neurons are found in the olfactory bulb mitral layer in 10 month old mice
• increase in dopaminergic neurons in olfactory bulb glomerular layer in 10 month old mice
• decreased numbers of cholinergic neurons are found in the olfactory bulb mitral layer in 10 month old mice

taste/olfaction
• time to locate buried food is increased in 6 and 10 month, but not 3 month, old mice as compared to wild-type