Phenotypes Associated with This Genotype

Genotype
MGI:5297859

• Allelic Composition: Tg(Prnp-SNCA*A53T)25Mkle/0
• Genetic Background: involves: C3H/HeJ * C57BL/6J

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

mortality/aging

premature death ( J:77344 )

• within 14-21 days of onset of motor problems and disease onset, mutants rapidly progress to death most likely due to inability to feed and drink

nervous system

abnormal nervous system morphology ( J:77344 )

• average age of onset of clinical abnormalities is 15.7 +/- 4.2 months, however 50% of mutants fail to develop disease at 24 months of age

• neuropathological abnormalities develop before motor dysfunction is visible

astrocytosis ( J:77344 )

• astroglial reaction is seen in the midbrain, deep cerebellar nuclei, brainstem and spinal cord, indicating neurodegeneration, but not in the cortex, hippocampus, thalamus, and caudate/putamen

abnormal neuron morphology ( J:77344 )

• mutants exhibit accumulation of ubiquitin and phosphorylated Nefh (NF-H) in perikarya and neurites

• affected neurons contain fibrillar inclusions

• abnormal neuronal accumulations are not seen in mutants younger than 4 months of age

neuronal intranuclear inclusions ( J:77344 )

• mutants exhibit accumulation of alpha-synuclein in neuronal cell bodies and neurites of the midbrain, cerebellum, brainstem and spinal cord

abnormal spinal cord morphology ( J:77344 )

• spinal cord exhibits astrocytic response and ubiquitin and alpha- synuclein accumulation in ventral horn motor neurons

neurodegeneration ( J:77344 )

• mutants develop adult-onset neurodegenerative disease

• astroglial reaction is seen in the midbrain, deep cerebellar nuclei, brainstem and spinal cord, indicating neurodegeneration

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:77344 )

• mutants develop motor signs characterized by sustained posturing, reduced amplitude, and abundance of spontaneous activity with age

impaired righting response ( J:77344 )

• mutants eventually develop progressive loss of righting reflex

dystonia ( J:77344 )

ataxia ( J:77344 )

bradykinesia ( J:77344 )

paralysis ( J:77344 )

• mutants eventually develop paralysis

muscle

dystonia ( J:77344 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease 1		DOID:0060367	OMIM:168601	J:77344