Phenotypes Associated with This Genotype

Genotype
MGI:3723272

• Allelic Composition: Tg(Prnp-SNCA*A53T)AAub/Tg(Prnp-SNCA*A53T)AAub
• Genetic Background: involves: FVB/N

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

behavior/neurological

impaired coordination ( J:86222 )

• up to 4 months of age, mutants perform better than controls on the accelerating rotating rod, but beyond 4 months, display progressive difficulties maintaining balance

decreased grip strength ( J:86222 )

• grip strength of forelimbs is significantly impaired (67 ponds) relative to controls (125 ponds)

weakness ( J:86222 )

• grip strength of forelimbs is significantly impaired (67 ponds) relative to controls (125 ponds)

short stride length ( J:86222 )

• step length of transgenic animals is reduced relative to wild-type (1.9 cm vs 2.25 cm in wild-type)

decreased vertical activity ( J:86222 )

• progressive reduction in rearing behavior is observed in animals at 6, 18, and 24 months of age, with notably decreased activity apparent at 3 months of age

nervous system

abnormal neurite morphology ( J:86222 )

• signs such as ballooning and kinky, tortuous, or corkscrew shapes of neurites are observed

alpha-synuclein inclusion body ( J:185489 )

• accumulation of human alpha-synuclein is seen in nerve terminals and cell bodies in the dorsal motor nucleus of the vagus nerve and in axon terminals innervating the gastric myenteric plexus, although accumulation is diffuse and does not show Lewy body-like appearance

neurodegeneration ( J:86222 )

• signs such as ballooning and kinky, tortuous, or corkscrew shapes of neurites are observed

• at 7 months of age, such abnormalities are seen only occasionally in the neocortex and hippocampus, but are frequently seen in a dense network of neurites in the olfactory bulb

absent long-term depression ( J:181820 )

• corticostriatal long-term depression (LTD) is absent in old, but not young, mutants

• dopamine does not restore LTD in old mice, however, zaprinast, an inhibitor of phosphodiesterases, restores LTD

• mice, however, do not exhibit age-related differences in striatal excitability

mortality/aging

premature death ( J:214065 )

• increased mortality rate in the first 180 days as compared to wild-type controls

digestive/alimentary system

abnormal defecation ( J:185489 )

• stool frequency is normal at 2 months of age but is 15%, 21%, and 40% lower at 9, 15, and 19 months of age, respectively

• total wet weight of stool and stool water content are lower in 19 month old mice compared to controls, however stool dry weight is no different and food intake and body weight are similar to controls

abnormal digestion ( J:185489 )

• mice show a decline in gastric emptying with age, with twice as much residual food remaining in the stomachs of 20 month old mutants as in controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease 1		DOID:0060367	OMIM:168601	J:181820 , J:185489