behavior/neurological phenotype

• bradykinesia
  • homozygotes display slow movements at 25-30 days of age
  (MGI Ref ID J:13411)

• abnormal stationary movement
  • homozygotes are first recognizable at 25-30 days of age when their movements become stiff, slow, and unstable
  (MGI Ref ID J:13411)

• abnormal posture
  • just prior to death, homozygotes cannot stand or walk and lie on their sides with all limbs extended
  (MGI Ref ID J:13411)

mammalian phenotype

• hearing/vestibular/ear phenotype
  • Normal - homozygotes display normal hearing
  (MGI Ref ID J:13411)

mortality/aging

• premature death
  • homozygotes become emaciated and die around 5 weeks of age
  (MGI Ref ID J:13411)

growth/size/body region phenotype

• decreased body size
  • all visceral organs appear normal but are uniformly smaller than normal
  (MGI Ref ID J:5025)
  • at 30 days of age or later, homozygotes are about 50%-75% the size of control littermates
  (MGI Ref ID J:5025)

• postnatal growth retardation
  • growth retardation is evident by 30 days of age
  (MGI Ref ID J:5025)

• cachexia
  • homozygotes exhibit significant wasting a few days prior to death
  (MGI Ref ID J:5025)

• decreased body height
  (MGI Ref ID J:5025)

mortality/aging

• premature death
  • homozygotes die between 5 and 6 weeks of age
  (MGI Ref ID J:5025)

muscle phenotype

• muscular atrophy
  • homozygotes display a uniform muscle atrophy, affecting all fibers; muscles of the lower half of the body appear wasted
  (MGI Ref ID J:5025)
  • fibers are closely packed within bundles
  (MGI Ref ID J:5025)
  • centrally located nuclei and nuclear rowing are observed
  (MGI Ref ID J:5025)

• opisthotonus
  (MGI Ref ID J:5025)

nervous system phenotype

• abnormal medulla oblongata morphology
  • medullary neurons are smaller than those of control littermates
  (MGI Ref ID J:5025)
  • the mutant medulla oblongata is smaller than that of controls and small relative to the size of the fore- and mibrain
  (MGI Ref ID J:5025)
  • the volume of both white and grey matter is reduced
  (MGI Ref ID J:5025)

• abnormal myelin sheath morphology
  • mutant myelin sheaths are smaller and thinner than those of control littermates, resulting in white matter reduction
  (MGI Ref ID J:5025)
  • Normal - however, no degeneration, total loss, or accumulation of myelin is observed
  (MGI Ref ID J:5025)

• abnormal spinal nerve morphology
  • mutant spinal nerves appear smaller than normal
  (MGI Ref ID J:5025)

• decreased midbrain size
  • Normal - in contrast, the overall size of the forebrain and its substructures is normal
  (MGI Ref ID J:5025)
  • the mutant midbrain is smaller than that of control littermates
  (MGI Ref ID J:5025)

• Purkinje cell degeneration
  • Purkinje cells of the cerebellum are variably reduced in number
  (MGI Ref ID J:5025)
  • shrunken Purkinje cells are observed
  (MGI Ref ID J:5025)
  • basket remnants persist around some cells but are eventually lost
  (MGI Ref ID J:5025)

• abnormal axon morphology
  • in both spinal cord and medulla, afferent axons are swollen but less often than in efferent tracts
  (MGI Ref ID J:5025)
  • in the medulla, axonal swellings appear as segmental or single coarse thickenings or bulbous-globular enlargements and occur primarily in efferent axons and most frequently in fibers of the tectospinal tract
  (MGI Ref ID J:5025)

• abnormal spinal cord grey matter morphology
  • neurons, glia and glial fibers of the grey matter, and spinal ganglia are smaller than normal
  (MGI Ref ID J:5025)
  • the funicular and short fiber tracts are smaller than normal
  (MGI Ref ID J:5025)
  • the mutant spinal cord is deficient in grey matter, with progressive severity caudally
  (MGI Ref ID J:5025)

• decreased spinal cord size
  • the mutant spinal cord is smaller and shorter than that of control littermates
  (MGI Ref ID J:5025)

• thin cerebellar granule layer
  • the mutant cerebellar granule cell layer is smaller than that of control littermates
  (MGI Ref ID J:5025)

• abnormal brain development
  • homozygotes display underdevelopment of certain brain regions
  (MGI Ref ID J:5025)
  • Normal - however, no heterotopia is observed
  (MGI Ref ID J:5025)

• abnormal CNS glial cell morphology
  • some neuroglia are significantly reduced in number and size while others remain normal
  (MGI Ref ID J:5025)

• decreased corticospinal tract size
  • the mutant pyramidal tract contains less fibers and is markedly smaller than that of control littermates and very small in proprtion to the medulla
  (MGI Ref ID J:5025)

• decreased neuron number
  • homozygotes show a disproportionate decrease in the size and number of neurons in the olivary and fastigial nuclei, spinal cord, and spinal ganglia
  (MGI Ref ID J:5025)

• small cerebellum
  • the mutant cerebellum is slightly smaller than that of control littermates
  (MGI Ref ID J:5025)
  • Normal - however, lobular formation and folia are normal
  (MGI Ref ID J:5025)
  • the volume of both white and grey matter is reduced
  (MGI Ref ID J:5025)

• axonal dystrophy
  • a few axonal swellings and abnormalities are seen in the medial lemniscus and corticospinal tract caudad to brain stem as well as the dorsal spinocerebellar tract
  (MGI Ref ID J:5025)
  • a mild axonal dystrophy is observed in the cerebellum, probably involving both the Purkinje cells and granule cell axons
  (MGI Ref ID J:5025)

• abnormal cerebellar cortex morphology
  • the mutant cerebellar cortex and most fiber tracts are reduced
  (MGI Ref ID J:5025)

• decreased hindbrain size
  • several structures of the mutant hindbrain are significantly reduced in size
  (MGI Ref ID J:5025)

• decreased pons size
  • the pons, trapezoid body, olivary and fastigial nuclei are significantly reduced in size
  (MGI Ref ID J:5025)

• abnormal spinal cord white matter morphology
  • the mutant spinal cord is deficient in white matter, with progressive severity caudally
  (MGI Ref ID J:5025)

skeleton phenotype

• short vertebral body
  (MGI Ref ID J:5025)

• abnormal vertebral spinous process morphology
  • mutant spinous processes are shorter than normal
  (MGI Ref ID J:5025)

• decreased trabecular bone thickness
  • mutant trabeculae and bony spicules are thinner and more delicate than normal
  (MGI Ref ID J:5025)

• abnormal vertebral column morphology
  • the diameter of the vertebral column is smaller than normal, esp. at the lumbar level of the spinal cord
  (MGI Ref ID J:5025)

behavior/neurological phenotype

• jerky movement
  • homozygotes tend to lurch and launch forward
  (MGI Ref ID J:5025)

• opisthotonus
  (MGI Ref ID J:5025)

• abnormal resting posture
  • homozygotes maintain an upright sitting position with their tail and hindlimbs, flexing their forelimbs close to the chest
  (MGI Ref ID J:5025)

• impaired balance
  (MGI Ref ID J:5025)

• increased stereotypic behavior
  • homozygotes repeatedly run in "fits", attepmt to climb the walls and fall over, with feet continuing to pedal vigorously
  (MGI Ref ID J:5025)

• paralysis
  • homozygotes eventually become paralyzed, are unable to stand and lay on their side with all limbs extended
  (MGI Ref ID J:5025)

• abnormal motor coordination/balance
  • at >30 days of age, homozygotes are unstable and walk stiffly
  (MGI Ref ID J:5025)

• impaired swimming
  • most homozygotes sink rapidly in water
  (MGI Ref ID J:5025)