Phenotypes Associated with This Genotype

Genotype
MGI:3723224

• Allelic Composition: Tg(PDGFB-SNCA)4Ema/0
• Genetic Background: involves: C57BL/6 * DBA/2

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

behavior/neurological

abnormal spatial learning ( J:166985 )

• during the spatial learning period of the water maze with the platform submerged, mutants exhibit show performance deficits compared with controls

• treatment of mice with the mGluR5 antagonist MPEP show improved performance in the water maze

• in the water maze probe test in which the platform was removed on the last day, mutants show differences in the entrances and passes into the target zone compared to controls; again, treatment with MPEP resulted in similar behavior to controls

increased thigmotaxis ( J:227112 )

• increase in thigmotaxis

• treatment with apomorphine, a compound that promotes dopamine releases, amelioration of thigmotaxis

abnormal motor coordination/balance ( J:166985 )

• mutants are impaired in ability to negotiate a pole apparatus as evidenced by a significantly longer T-turn time

• treatment of mice with a mGluR5 antagonist MPEP results in an improvement in T-turn time

impaired coordination ( J:60638 , J:227112 )

• mice show deficits in motor performance in the rotorod test compared to wild-type mice (J:60638)

• mice at 12 months of age show mild to moderate motor deficits on the rotarod (J:227112)

homeostasis/metabolism

decreased dopamine level ( J:227112 )

• dopamine levels in the caudoputamen region are decreased by 25-50% at 12 months of age

nervous system

loss of dopaminergic neurons ( J:60638 )

neuronal intranuclear inclusions ( J:60638 )

• prominent cytoplasmic and nuclear inclusions immunoreactive to human alpha-synuclein are observed by 2 months of age; these are most frequent in neurons of the deep neocortex, CA3 region of the hippocampus, olfactory bulb and occasionally the substantia nigra

• in 9-11 month old mice, larger inclusions composed of fine granular material are seen, and contain clear vacuoles

alpha-synuclein inclusion body ( J:137490 )

• alpha-synuclein protein accumulates in synapses and neurons throughout the brain, including the neuropil of presynaptic terminals, neocortex, hippocampus, cerebellum, substantia nigra, limbic system, and olfactory regions, and inclusion bodies form in neurons in the deeper layers of the neocortex and in axons

• alpha-synuclein protein accumulation is also seen in the glial cells along the white matter tracts in the colliculus, thalamus, brainstem, hippocampus, and cerebellum

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Lewy body dementia		DOID:12217	OMIM:127750	J:60638 , J:137490 , J:166985
Parkinson's disease 1		DOID:0060367	OMIM:168601	J:60638 , J:166985