Phenotypes Associated with This Genotype

Genotype
MGI:5632508

• Allelic Composition: Tg(THY1-SNCA*A53T)M53Sud/0
• Genetic Background: B6.Cg-Tg(THY1-SNCA*A53T)M53Sud/J

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

mortality/aging

premature death ( J:212732 )

• most mice die between 10 and 12 months of age

behavior/neurological

tremors ( J:212732 )

• mice begin to show tremors around 6 months of age

ataxia ( J:212732 )

• mice at 6 months of age show motor activity deficits and 100% of mice at 1 year of age develop rigidity, postural instability, and immobility

jerky movement ( J:212732 )

• seen around 8 months of age

abnormal posture ( J:212732 )

• mice at 1 year of age show postural instability

abnormal gait ( J:212732 )

• mice develop gait abnormalities, such as jerky movements at around 8 months of age

bradykinesia ( J:212732 )

• mice develop bradykinesia at around 8 months of age and show progressive deterioration of motor activity to complete immobility by 12 months of age

spasticity ( J:212732 )

• mice begin to show spasticity around 6 months of age

nervous system

increased neuron apoptosis ( J:212732 )

• apoptosis of nigral neurons and cortical neruons

abnormal nervous system morphology ( J:212732 )

• agyrophilic degeneration in the red nucleus, superior cerebellar peduncle, medial lemniscus, and cerebral peduncle

abnormal brain interneuron morphology ( J:212732 )

• striatal interneuron degeneration

• cerebellar interneurons degenerate early in the course of disease

abnormal midbrain morphology ( J:212732 )

• degeneration of the ventral midbrain

abnormal substantia nigra pars compacta morphology ( J:212732 )

• about 60% loss of neurons in the substantia nigra pars compacta

abnormal red nucleus morphology ( J:212732 )

• apoptotic cells and loss of magnocellular neurons are seen in the red nucleus at endstage disease

abnormal thalamus morphology ( J:212732 )

• motor thalamus degeneration; nuclear-specific degeneration is seen in the ventral anterior and ventrolateral nucleus thalamic nuclei and the central medial, central lateral, and paracentral thalamic nuclie are also affected

abnormal thalamus neuron morphology ( J:212732 )

• approximate 40% loss of neurons in the ventral anterior and/or ventral lateral thalamic nuclei of 12 month old mice

abnormal hippocampus layer morphology ( J:212732 )

• modest neuropil punctate degeneration in the stratum radiatum of CA3 and stratum lacunosum-moleculare of CA1 of the hippocampus

abnormal cerebral cortex morphology ( J:212732 )

• degeneration of the cerebral cortex

• ventricular system in the cerebral cortex is dilated at endstage disease

• thinning of the cortical mantle

• cell death is increased in layer V of the cerebral cortex at 8 and 12 months of age

abnormal cerebral cortex pyramidal cell morphology ( J:212732 )

• enhanced autophagy in cortical pyramidal neurons

abnormal cerebellum morphology ( J:212732 )

• reduction in the thickness of the sensorimotor cortical gray matter

• mice at endstage disease show degeneration of the deep cerebellar nuclei

abnormal cerebellum white matter morphology ( J:212732 )

• reduction in the thickness of the subcortical white matter

abnormal superior cerebellar peduncle morphology ( J:212732 )

• agyrophilic degeneration in the superior cerebellar peduncle

abnormal cerebellar layer morphology ( J:212732 )

• degenerating cell bodies are seen in the granule cell layer, apoptotic cells in the molecular layers and terminal degeneration at the granule cell layer-Purkinje cell layer border as early as 1 month of age

abnormal cerebellum interpositus nucleus morphology ( J:212732 )

• degeneration of cerebellar interpositus nucleus

neuron degeneration ( J:212732 )

• nigral neuron degeneration, with about 60% loss of neurons

• apoptotic degeneration of interneurons of young mice, with degeneration of striatal and cerebellar interneurons

• about 60% loss of red nucleus neurons at endstage disease

• approximate 40% loss of neurons in the ventral anterior and/or ventral lateral thalamic nuclei of 12 month old mice

neuronal cytoplasmic inclusions ( J:212732 )

• some degenerating substantia nigra pars compacta neurons show cytoplasmic Lewy-body-like inclusions

alpha-synuclein inclusion body ( J:212732 )

• cortical neurons show cytoplasmic and intranuclear aggregates of human synuclien protein

axon degeneration ( J:212732 )

• axonal degeneration in the cortical gray matter and subcortical white matter and in the cerebral peduncle

• axonal and punctate degeneration in the red nucleus and intermingling superior cerebellar peduncle

cellular

increased neuron apoptosis ( J:212732 )

• apoptosis of nigral neurons and cortical neruons

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease 1		DOID:0060367	OMIM:168601	J:212732