behavior/neurological phenotype

• short stride length
  • at 18 months, mice have shorter strides than wild-type mice
  (MGI Ref ID J:147580)

• impaired coordination
  • after 18 months of age, mice exhibit impaired performance on a rotarod compared with wild-type mice
  (MGI Ref ID J:147580)

• abnormal motor coordination/balance
  • mice develop motor dysfunction compared with wild-type mice with greater latency and slower progression than homozygous mice
  (MGI Ref ID J:147580)

homeostasis/metabolism phenotype

• amyloidosis
  • the number of inclusions increases as clinical phenotypes worsen
  (MGI Ref ID J:147580)
  • in the spinal cord or brain tissue when mild clinical signs of pathology are apparent
  (MGI Ref ID J:147580)

nervous system phenotype

• decreased motor neuron number
  • motor neuron loss corresponds to severity of motor impairment
  (MGI Ref ID J:147580)

• astrocytosis
  • in older mice
  (MGI Ref ID J:147580)

hematopoietic system phenotype

• microgliosis
  • observed in the trigeminal motor nucleus in affected 12 month old mice
  (MGI Ref ID J:185793)

immune system phenotype

• microgliosis
  • observed in the trigeminal motor nucleus in affected 12 month old mice
  (MGI Ref ID J:185793)

mammalian phenotype

• nervous system phenotype
  • Normal - retinal ganglion cells do not exhibit deterioration or loss despite overexpression of gamma-synuclein
  (MGI Ref ID J:185793)

nervous system phenotype

• abnormal sciatic nerve morphology
  • mildly affected mice exhibit slight changes in morphology, but no loss of fibers
  (MGI Ref ID J:185793)
  • reduced levels of neurofilament proteins, alpha tubulin, and myelin basic protein are observed in severely affected mice
  (MGI Ref ID J:185793)
  • active Wallerian-like degeneration of the sciatic nerve is observed
  (MGI Ref ID J:185793)
  • deterioration and loss of myelinated axons in severely affected mice
  (MGI Ref ID J:185793)
  • reduction in total numbers of myelinated fibers in severely affected mice
  (MGI Ref ID J:185793)

• abnormal trigeminal nerve morphology
  • significant neuron loss is observed in affected 12 month old mice
  (MGI Ref ID J:185793)
  • mice exhibit high levels of astrogliosis and microgliosis in the trigeminal motor nucleus
  (MGI Ref ID J:185793)

• abnormal ventral spinal root morphology
  • deterioration and loss of myelinated fibers in severely affected mice
  (MGI Ref ID J:185793)
  • significant decrease in mean myelinated fiber size (49.5%) found in remaining myelinated fibers
  (MGI Ref ID J:185793)
  • extensive phagocyte infiltration
  (MGI Ref ID J:185793)

• astrocytosis
  • observed in the trigeminal motor nucleus in affected 12 month old mice
  (MGI Ref ID J:185793)

• decreased motor neuron number
  • loss of motor neurons is observed in the trigeminal motor nucleus, but not in the facial and abducens motor nuclei
  (MGI Ref ID J:185793)
  • neuron loss is correlated with perikaryal and axonal accumulation of gamma-synuclein, accumulation of detergent-insoluble species and gliosis
  (MGI Ref ID J:185793)
  • neuron loss is observed in select upper and lower motor neuron populations of the motor cortex, and to a lesser degree in the somatosensory regions
  (MGI Ref ID J:185793)

• gliosis
  • gliosis is observed within motor regions of cortex
  (MGI Ref ID J:185793)

• microgliosis
  • observed in the trigeminal motor nucleus in affected 12 month old mice
  (MGI Ref ID J:185793)

• abnormal myelin sheath morphology
  • damage to myelin sheath is observed in substantial numbers of myelinated fibers from the sciatic nerve in severely affected mice
  (MGI Ref ID J:185793)

• abnormal dorsal spinal root morphology
  • however, the majority of myelinated fibers are similar to control in number and condition
  (MGI Ref ID J:185793)
  • some abnormal myelinated fibers and phagocytes are observed in the dorsal spinal root
  (MGI Ref ID J:185793)

• neuron degeneration
  • selective neuronal dystrophy is observed in the cortex
  (MGI Ref ID J:185793)

homeostasis/metabolism phenotype

• amyloidosis
  • in the spinal cord or brain tissue when mild clinical signs of pathology are apparent
  (MGI Ref ID J:147580)
  • the number of inclusions increases as clinical phenotypes worsen
  (MGI Ref ID J:147580)

mortality/aging

• premature death
  • mice do not survive beyond 16 months
  (MGI Ref ID J:147580)

nervous system phenotype

• abnormal nervous system morphology
  • abnormal gamma-synuclein structures are most abundant in the spinal cord
  (MGI Ref ID J:147580)
  • mice exhibit aggregation and fibrillation of gamma-synuclein in the nervous system unlike wild-type mice
  (MGI Ref ID J:147580)

• decreased motor neuron number
  • motor neuron loss corresponds to severity of motor impairment
  (MGI Ref ID J:147580)
  • at 12 months, motor neuron numbers in severely affected mice are less than 40% of wild-type
  (MGI Ref ID J:147580)

• astrocytosis
  • in the spinal cord gray matter of severely affected and older mice
  (MGI Ref ID J:147580)

behavior/neurological phenotype

• abnormal motor coordination/balance
  (MGI Ref ID J:147580)

• abnormal gait
  • at 6 to 9 months
  (MGI Ref ID J:147580)

• impaired coordination
  • earlier than 6 months
  (MGI Ref ID J:147580)

• limb grasping
  • at 6 to 9 months
  (MGI Ref ID J:147580)

• impaired righting response
  • following paresis
  (MGI Ref ID J:147580)

• short stride length
  • at 6 months
  (MGI Ref ID J:147580)

• hunched posture
  • at 6 to 9 months
  (MGI Ref ID J:147580)

• impaired balance
  • earlier than 6 months
  (MGI Ref ID J:147580)

• paralysis
  • following paresis
  (MGI Ref ID J:147580)

• paresis
  • at 9 to 16 months, mice develop paresis unlike wild-type mice with earlier development in forelimbs than in hindlimbs
  (MGI Ref ID J:147580)