nervous system phenotype

• decreased Purkinje cell number
  • total number of Purkinje cells is less than normal by 10 days of age
  (MGI Ref ID J:24754)

• small cerebellum
  • although smaller than normal, the cerebellum has a normal folial pattern
  (MGI Ref ID J:24754)

• abnormal Purkinje cell differentiation
  • Purkinje cell nuclei are often eccentrically positioned
  (MGI Ref ID J:6464)
  • cerebeller Purkinje cells fail to mature and have swellings along the larger dendritic trunks, especially at the branch points, and short, spiny dendrites projecting from all parts of the soma
  (MGI Ref ID J:6464)
  • an increase in the number of mitochondrial profiles in Purkinje cell soma even at 10 days of age
  (MGI Ref ID J:6464)

• abnormal Purkinje cell morphology
  • Purkinje cells have reduced total volume, irregularly increased caliber, abnormal branching patterns of dendrites, high concentration of mitochondria in soma and dendrites, persistent somatic spines and filopodia at least to 21 days of age, and focal swellings on axons
  (MGI Ref ID J:24754)
  • lings on axons
  (MGI Ref ID J:24754)

• abnormal Purkinje cell dendrite morphology
  (MGI Ref ID J:24754)

• abnormal cerebellar granule cell morphology
  • total number of granule cells is less than normal by 10 days of age
  (MGI Ref ID J:24754)
  • some granule cells appear to have longer than normal dendrites
  (MGI Ref ID J:6464)

behavior/neurological phenotype

• abnormal righting response
  • the righting response is delayed by a day or two so young homozygote have greater than normal difficulty in turning onto their feet
  (MGI Ref ID J:6464)

• abnormal gait
  • high stepping broad-based gait, stumbling locomotion found by 12 days of age
  (MGI Ref ID J:6464)

cellular phenotype

• abnormal Purkinje cell differentiation
  • an increase in the number of mitochondrial profiles in Purkinje cell soma even at 10 days of age
  (MGI Ref ID J:6464)
  • Purkinje cell nuclei are often eccentrically positioned
  (MGI Ref ID J:6464)
  • cerebeller Purkinje cells fail to mature and have swellings along the larger dendritic trunks, especially at the branch points, and short, spiny dendrites projecting from all parts of the soma
  (MGI Ref ID J:6464)

growth/size/body region phenotype

• decreased body weight
  • homozygotes become less active, never gain as much weight as littermate controls, and this weight disparity is progressive
  (MGI Ref ID J:6464)

mortality/aging

• postnatal lethality
  • Background Sensitivity - on the C3H/HeJ background homozygotes die by 21 days of age, but live slightly longer when crossed with C57BL/6J
  (MGI Ref ID J:24754)
  • most homozygotes die before weaning
  (MGI Ref ID J:6464)

growth/size/body region phenotype

• decreased body weight
  • as early as 9 days of age homozygotes are approximately 15% lighter than controls and by 23 days of age weigh only 40% that of controls
  (MGI Ref ID J:28094)

nervous system phenotype

• thin cerebellar molecular layer
  • slightly thinner than normal at 10 to 23 days of age
  (MGI Ref ID J:28094)

• abnormal cerebellar granule layer morphology
  (MGI Ref ID J:28094)

• thin cerebellar granule layer
  • slightly thinner than normal from 10 to 23 days of age, and the volume of the granule layer is reduced in older homozygotes
  (MGI Ref ID J:28094)

• Purkinje cell degeneration
  • degenerating Purkinje cells are only seen after 19 days of age
  (MGI Ref ID J:28094)

• small cerebellum
  • after 10 days of age the cerebellum ceases to grow at the same rate as controls, which show rapid cerebellar growth overthe first 3 weeks of life, and thus the stumbler cerebellum is smaller than normal
  (MGI Ref ID J:28094)
  • the smaller cerebellum is due primarily to a comparative reduction in number of Purkinje cells and granule cells
  (MGI Ref ID J:28094)

• thin external granule cell layer
  • slightly thinner than normal at 10 to 13 days of age
  (MGI Ref ID J:28094)

• abnormal Purkinje cell morphology
  • Purkinje cells have disorganized endoplasmic reticulum and an increased number of mitochondria, although normal-looking synapses are found, and in homozygotes that live to 35 days of age near-normal looking Purkinje cells can be found
  (MGI Ref ID J:28094)

• abnormal cerebellar molecular layer
  (MGI Ref ID J:28094)

• decreased Purkinje cell number
  • Purkinje cells never reach normal numbers
  (MGI Ref ID J:28094)

• abnormal cerebellar cortex morphology
  • the length of all of the layers of the cerebellar cortex is shorter than normal
  (MGI Ref ID J:28094)

• abnormal cerebellar Purkinje cell layer
  (MGI Ref ID J:28094)

• abnormal Purkinje cell dendrite morphology
  • at 9 days of age Purkinje cells have dendritic arborizations that appear immature, are much smaller than normal, and have somatic spines which can still be found at 23 days of age
  (MGI Ref ID J:28094)

mammalian phenotype

• nervous system phenotype
  • Normal - the foliation of the cerebellar cortex is normal even though the size is small
  (MGI Ref ID J:28094)