mammalian phenotype

• behavior/neurological phenotype
  • Normal - homozygotes respond normally to painful stimuli in their whisker pads as well as to pinching of their tail and foot
  (MGI Ref ID J:17195)

mortality/aging

• postnatal lethality
  • most homozygotes die by P21
  (MGI Ref ID J:17195)

• premature death
  • a few homozygotes live up to 4 months or longer
  (MGI Ref ID J:17195)

nervous system phenotype

• abnormal lumbar dorsal root ganglion morphology
  • newborn homozygotes show a 19% neuron loss in the lumbar dorsal root ganglia
  (MGI Ref ID J:17195)

• small cochlear ganglion
  • large-sized type I neurons (innervating IHCs) are preferentially lost (62% reduction), whereas small-sized type II neurons (innervating OHCs) remain unaffected
  (MGI Ref ID J:29245)
  • at P1, a 51% reduction in cochlear ganglion neuron number is observed
  (MGI Ref ID J:29245)

• small vestibular ganglion
  • by P1, a 16% reduction in vestibular ganglion neuron number is observed
  (MGI Ref ID J:29245)
  • Normal - however, both vestibular ganglia and vestibular sensory epithelia are histologically normal and their innervation patterns appear unaffected
  (MGI Ref ID J:29245)

• abnormal cochlear IHC afferent innervation pattern
  • at P1, IHCs are devoid of innervation
  (MGI Ref ID J:29245)
  • developmental analysis indicates that, at E16.5, some cochlear nerve fibers initially reach their peripheral targets but subsequently fail to maintain innervation and degenerate
  (MGI Ref ID J:29245)
  • in contrast, the innervation pattern of OHCs appears normal
  (MGI Ref ID J:29245)

• abnormal sensory neuron innervation pattern
  • homozygotes lack Ia muscle afferent projections to spinal motor neurons and have fewer large myelinated axons in the dorsal root and posterior columns of the spinal cord
  (MGI Ref ID J:17195)

behavior/neurological phenotype

• impaired coordination
  • on a rotating dowel, homozygotes fail to maintain an upright posture and tumble off
  (MGI Ref ID J:17195)

• impaired limb coordination
  • even at rest, the limbs are held in abnormal positions in relation to the trunk
  (MGI Ref ID J:17195)

• limb grasping
  • when hung by the tail, homozygotes draw their limbs in towards their bodies
  (MGI Ref ID J:17195)

• athetotic walking movements
  • by P10, homozygotes display athetotic walking movements
  (MGI Ref ID J:17195)

growth/size/body region phenotype

• decreased body size
  • although normal at birth, homozygotes exhibit reduced body size at P4
  (MGI Ref ID J:17195)

hearing/vestibular/ear phenotype

• abnormal cochlear IHC afferent innervation pattern
  • developmental analysis indicates that, at E16.5, some cochlear nerve fibers initially reach their peripheral targets but subsequently fail to maintain innervation and degenerate
  (MGI Ref ID J:29245)
  • at P1, IHCs are devoid of innervation
  (MGI Ref ID J:29245)
  • in contrast, the innervation pattern of OHCs appears normal
  (MGI Ref ID J:29245)

• abnormal cochlear sensory epithelium morphology
  • at P1, the cochlear sensory epithelium appears thinner and less stratified than normal
  (MGI Ref ID J:29245)