Phenotypes Associated with This Genotype

Genotype
MGI:5544308

• Allelic Composition: Snca^tm1Rosl/Snca^tm1Rosl; Tg(SNCA)OVX37Rwm/0
• Genetic Background: B6.Cg-Tg(SNCA)OVX37Rwm Snca^tm1Rosl

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

behavior/neurological

impaired coordination ( J:201991 )

• 18 month old mutants show a reduced latency to fall on the rotarod test and are impaired on the multiple static rods test

• however, no differences in the latency to fall in the inverted screen test is seen

short stride length ( J:201991 )

• reduction in forepaw stride length in 18 month old mutants

digestive/alimentary system

constipation ( J:201991 )

♂ • dry stool weight is increased in males but not females, independent of age; however, stool frequency and stool water content are normal, indicating constipation-like phenotype

homeostasis/metabolism

increased dopamine level ( J:201991 )

• net dopamine content is unchanged in caudate putamen or nucleus accumbens at 3-4 and 12 months of age, however at 18 months of age, dopamine content is greater in the caudate putamen

nervous system

abnormal dopaminergic neuron morphology ( J:201991 )

• vesicles in dopamine axons of the dorsal striatum are more clustered than in controls at 3 months of age; the frequency distribution of intervesicle distance is reduced and vesicles are 3 times less dispersed

loss of dopaminergic neurons ( J:201991 )

• 18 month old mutants exhibit loss of substantia nigra pars compacta dopamine neurons

neuron degeneration ( J:201991 )

• 18 month old mutants exhibit loss of substantia nigra pars compacta dopamine neurons

• however, aggregation of alpha-synuclein is not seen in the substantia nigra pars compacta or striatum

abnormal neuron physiology ( J:201991 )

• substantia nigra pars compacta dopamine neurons exhibit age-dependent reductions (almost 30%) in firing rates in vivo

abnormal synaptic dopamine release ( J:201991 )

• in the dorsal striatum, mean peak extracellular concentrations of dopamine evoked by single electrical pulses across distributed recording sites are on average about 30% lower than in controls; this reduced release is seen from a young age of 3-4 months before the loss of dopamine neurons and persists throughout their lifespan

• greatest deficits in dopamine release are seen in the dorsal and lateral striatum

• the dopamine release deficit persists in the presence of nicotinic receptor blockade by dihydro-beta-erythroidine

• dopamine uptake kinetics are normal and norepinephrine and 5-hydroxytryptamine axonal release are normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease 1		DOID:0060367	OMIM:168601	J:201991