Phenotypes Associated with This Genotype

Genotype
MGI:5573196

• Allelic Composition: Tg(Thy1-Snca)1S13Putt/?
• Genetic Background: involves: C57BL/6

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

nervous system

microgliosis ( J:177661 )

abnormal brainstem morphology ( J:177661 )

• brainstem shows pronounced ubiquitin imunopathology

astrocytosis ( J:177661 )

abnormal neuron morphology ( J:177661 )

• neurofilaments are short, thick, and less well oriented of about 10 nm in diameter, devoid of side-branches and coincide with non-fibrillar amorphous aggregates

abnormal axon morphology ( J:177661 )

• central axons are often enlarged

abnormal dendrite morphology ( J:177661 )

• ubiquitin immunoreactive motor neurons have spindle-shaped dilated proximal dendrites

abnormal neuromuscular synapse morphology ( J:177661 )

• neuromuscular synapses show signs of presynaptic degeneration that is independent of muscle fiber type

• neuromuscular junctions show thinning or absence of presynaptic neurofilaments

abnormal spinal cord morphology ( J:177661 )

• spinal cord shows pronounced ubiquitin imunopathology

abnormal motor neuron morphology ( J:177661 )

• ubiquitin immunoreactive motor neurons have spindle-shaped dilated proximal dendrites

alpha-synuclein inclusion body ( J:177661 , J:207278 )

• alpha-synuclein non-fibrillar amorphous aggregates (J:177661)

• multiple isoforms of alpha synuclein are seen, including serine 129 phosphorylated species in the most severely affected brain regions (J:177661)

• neuronal serine 129 phosphorylated form of alpha-synuclein is seen in granular and small fibrillar aggregates and neurites show alternating segments of either alpha-synuclein or ubiquitin but not both (J:177661)

• increase in perikaryal alpha-synuclein accumulation in the cell soma of hippocampal neurons (J:207278)

axon degeneration ( J:177661 )

• axonal degeneration in long white matter tracts of the spinal cord with breakdown of myelin sheaths into rows of myelin ovoids

demyelination ( J:177661 )

• long white matter tracts of the spinal cord show breakdown of myelin sheaths into rows of myelin ovoids

• loosening of the myelin wraps and vesicular disruption of the myelin sheath

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:177661 )

• around 6-7 months of age, mice start to display severe motor deficits, indicating late-onset motor impairment

impaired coordination ( J:177661 )

• during the first 4 weeks of age, mice show impaired motor learning on the accelerated rotarod task, but by 12 weeks of age and after a number of training sessions, performance is normal up to 6 months of age

• from 6-7 months of age onwards, mice show a steady and rapid decline in rotarod performance

• mice however show normal behavior in the open field, normal activity in the dark-light box and elevated plus maze, indicating no anxiety, and normal forelimb grip strength

cellular

increased mitochondrial size ( J:177661 )

• enlarged mitochondria with an abnormally high number of cristae without obvious vacuolization in spinal cord dendrites

growth/size/body

decreased body weight ( J:177661 )

• around 6-7 months of age, mice stop gaining weight

hematopoietic system

microgliosis ( J:177661 )

immune system

microgliosis ( J:177661 )

mortality/aging

premature death ( J:177661 )

• increase in mortality

muscle

abnormal muscle fiber morphology ( J:177661 )

• muscles contain small angulated fibers reminiscent of neurogenic muscular atrophy

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease 4		DOID:0060895	OMIM:605543	J:177661