nervous system phenotype

• abnormal axon morphology
  • axonal swelling and degeneration are seen but less frequently than in hemizygous males; however all optic nerve axons have normal myelin sheaths
  (MGI Ref ID J:48031)

behavior/neurological phenotype

• abnormal locomotor coordination
  • at 16 months of age impaired performance in a rotarod test is seen
  (MGI Ref ID J:48031)

• impaired coordination
  • at 16 months of age impaired performance in a rotarod test is seen
  (MGI Ref ID J:48031)

• abnormal gait
  • older mice develop a slow gait
  (MGI Ref ID J:48031)

nervous system phenotype

• demyelination
  • evidence of demyelination is seen at 22 months of age
  (MGI Ref ID J:48031)

• astrocytosis
  • mild astrocytosis accompanies degenerative changes
  (MGI Ref ID J:48031)
  • moderate, but significant, astrogliosis in the hippocampal fimbria at 26 weeks of age
  (MGI Ref ID J:245100)

• axonal spheroids
  • APP+ axonal spheroids are present in the hippocampal fimbria and corpus callosum at 26 weeks of age
  (MGI Ref ID J:245100)

• abnormal myelin sheath morphology
  • in areas of axonal swelling the myelin sheath becomes attenuated and is eventually lost though slippage
  (MGI Ref ID J:48031)
  • decrease in cholesterol content
  (MGI Ref ID J:193310)

• abnormal axon morphology
  • at 6 - 8 weeks, focal axonal swellings containing organelles are seen mostly in areas where small diameter axons predominate throughout the white and gray matter
  (MGI Ref ID J:48031)
  • by 1 year, numerous large axonal swellings are seen in the optic nerve and spinal cord with some also seen in Purkinje cell axons
  (MGI Ref ID J:48031)
  • after 1 year, axonal degeneration is seen in the optic nerve and fasciculus gracilis; however, no signs of peripheral neuropathy are seen
  (MGI Ref ID J:48031)

• microgliosis
  • microgliosis in the hippocampal fimbria at 26 weeks of age
  (MGI Ref ID J:245100)

• abnormal oligodendrocyte morphology
  • primary glial cultures have increased numbers of oligodendrocytes starting at the second division and persisting through at least the fourteenth division; however no increase in oligodendrocyte proliferation is seen
  (MGI Ref ID J:106182)
  • occasionally inner tongue processes of pligdendrocytes contain degenerated organelles
  (MGI Ref ID J:48031)
  • in primary glial cultures oligodendrocyte sheets appear larger, vacuolated, and broken suggesting decreased stability of the myelin sheet
  (MGI Ref ID J:106182)

• abnormal microglial cell morphology
  • increased numbers of microglia accompany degenerative changes
  (MGI Ref ID J:48031)

• abnormal hippocampal fimbria morphology
  • hippocampal fimbria exhibits APP+ axonal spheroids, microgliosis and astrogliosis
  (MGI Ref ID J:245100)

hematopoietic system phenotype

• microgliosis
  • microgliosis in the hippocampal fimbria at 26 weeks of age
  (MGI Ref ID J:245100)

• abnormal microglial cell morphology
  • increased numbers of microglia accompany degenerative changes
  (MGI Ref ID J:48031)

homeostasis/metabolism phenotype

• decreased cholesterol level
  • in myelin
  (MGI Ref ID J:193310)

immune system phenotype

• microgliosis
  • microgliosis in the hippocampal fimbria at 26 weeks of age
  (MGI Ref ID J:245100)

• abnormal microglial cell morphology
  • increased numbers of microglia accompany degenerative changes
  (MGI Ref ID J:48031)

nervous system phenotype

• tomacula
  (MGI Ref ID J:236408)

• axonal spheroids
  (MGI Ref ID J:236408)

• dysmyelination
  • hypomyelination with split myelin lamellae
  (MGI Ref ID J:236408)

behavior/neurological phenotype

• hindlimb paralysis
  • at 40 weeks of age
  (MGI Ref ID J:201143)

skeleton phenotype

• kyphosis
  • at 40 weeks of age
  (MGI Ref ID J:201143)

growth/size/body region phenotype

• decreased body weight
  • at 4 and 40 weeks of age
  (MGI Ref ID J:201143)

hematopoietic system phenotype

• microgliosis
  • low grade in the hippocampal fimbria
  (MGI Ref ID J:201143)

immune system phenotype

• microgliosis
  • low grade in the hippocampal fimbria
  (MGI Ref ID J:201143)

nervous system phenotype

• demyelination
  • moderately dysmyelinated due to diminished myelination of axons with the smallest calibers, significant at 40 weeks of age
  (MGI Ref ID J:201143)

• astrocytosis
  • mild astrogliosis in the hippocampal fimbria
  (MGI Ref ID J:201143)

• axon degeneration
  • density of axons shows a striking reduction to fewer than half that of controls
  (MGI Ref ID J:201143)

• axonal spheroids
  (MGI Ref ID J:201143)

• microgliosis
  • low grade in the hippocampal fimbria
  (MGI Ref ID J:201143)

behavior/neurological phenotype

• paraparesis
  • weakness particularly of the hind limbs develops by 18 months of age
  (MGI Ref ID J:146665)

• ataxia
  • gait ataxia is seen by 18 months of age
  (MGI Ref ID J:146665)

nervous system phenotype

• abnormal axon morphology
  • swollen axons are seen
  (MGI Ref ID J:146665)

• axon degeneration
  • at 8 months of age occasional degenerating fibers are seen in the cervical region of the fasciculus gracilis
  (MGI Ref ID J:146665)
  • at 18 months of age pronounced axonal degeneration is seen in the cervical segments in the thoracic region but not in the lumbar dorsal columns
  (MGI Ref ID J:146665)

• abnormal myelin sheath morphology
  • Normal - however, in non swollen regions sheaths are of normal thickness
  (MGI Ref ID J:146665)
  • some attenuated myelin sheaths are seen around swollen axons
  (MGI Ref ID J:146665)

mammalian phenotype

• behavior/neurological phenotype
  • Normal - no signs of motor dysfunction or impaired coordination are detected
  (MGI Ref ID J:38856)

nervous system phenotype

• axonal spheroids
  • in mice over 2 months of age, some axonal spheroids
  (MGI Ref ID J:38856)

• abnormal myelin sheath morphology
  • myelin is compacted but the distinction between major dense lines and intraperiod lines is less than in wild-type; however, the proportion of myelinated axons, myelin sheath thickness and size range of myelinated fibers are similar to wild-type
  (MGI Ref ID J:38856)
  • in a few areas double intraperiod lines are seen and myelin sheaths are more susceptible to damage during the fixation process compared to wild-type
  (MGI Ref ID J:38856)