nervous system phenotype

• abnormal cerebellar molecular layer
  • molecular layer thickness is decreased at P15 and P30, but not at later stages, suggesting a developmental delay
  (MGI Ref ID J:230904)
  • Normal - however, mice do not exhibit cerebellar neurodegeneration or Purkinje cell loss with age
  (MGI Ref ID J:230904)

• abnormal neuron physiology
  • Purkinje cell firing is already compromised in pre-weaned developing pups, with Purkinje cells firing more rapidly and with even less regularity than controls
  (MGI Ref ID J:230904)
  • Purkinje cells fire erratically on the whole, however they also exhibit higher regularity during firing
  (MGI Ref ID J:230904)
  • chlorzoxazone, a muscle relaxant, corrects several properties of Purkinje cell firing
  (MGI Ref ID J:230904)
  • Purkinje cell activity is severely impaired, with Purkinje cells firing with long pauses
  (MGI Ref ID J:230904)

• abnormal cerebellum morphology
  • the patterning of the cerebellum into zones is spatially and temporally altered
  (MGI Ref ID J:230904)

• abnormal innervation
  • chlorzoxazone does not reconfirgure the miswired cerebellar circuit map
  (MGI Ref ID J:230904)
  • cuneocerebellar and spinocerebellar proprioceptive pathways exhibit overlapping domains
  (MGI Ref ID J:230904)
  • the wiring of cerebellar sensory maps is poorly coordinated
  (MGI Ref ID J:230904)
  • the adult spinocerebellar sensory map is not sharply delineated, with the topography of the afferent map less clear at P90 compared to P30
  (MGI Ref ID J:230904)

behavior/neurological phenotype

• tremors
  • mice develop a severe tremor with age
  (MGI Ref ID J:230904)
  • as tremor amplitude increases with age, the frequency decreases
  (MGI Ref ID J:230904)

• abnormal gait
  • this mutant has an odd waddling walk throughout life
  (MGI Ref ID J:81344)

• ataxia
  • side-to-side movements are obvious by 2 weeks of age
  (MGI Ref ID J:103673)

• impaired coordination
  • motor performance on the rotarod declines with age
  (MGI Ref ID J:230904)
  • chlorzoxazone treatment improves motor performance on the rotarod, although it does not completely rescue the phenotype to control levels
  (MGI Ref ID J:230904)

• abnormal motor learning
  • motor learning on the rotarod improves at P30 but not over the 12 trials at P90 or P360
  (MGI Ref ID J:230904)

hearing/vestibular/ear phenotype

• abnormal auditory brainstem response
  • Background Sensitivity - hearing of mutant and control is abnormal by 7 months of age due to C57BLKS/J background
  (MGI Ref ID J:81344)