nervous system phenotype

• abnormal cerebellum vermis lobule III morphology
  • significant decrease in the surface area
  (MGI Ref ID J:130259)

• abnormal cerebellum vermis lobule morphology
  (MGI Ref ID J:130259)

• abnormal cerebellum vermis lobule II morphology
  • significant decrease in the surface area
  (MGI Ref ID J:130259)

• abnormal cerebellum vermis lobule IV morphology
  • significant decrease in the surface area
  (MGI Ref ID J:130259)

• abnormal cerebellum vermis lobule VII morphology
  • significant decrease in the surface area
  (MGI Ref ID J:130259)

• abnormal cerebellum vermis lobule VI morphology
  • significant decrease in the surface area
  (MGI Ref ID J:130259)

• abnormal cerebellum vermis lobule V morphology
  • significant decrease in the surface area
  (MGI Ref ID J:130259)

behavior/neurological phenotype

• abnormal nest building behavior
  • significant impairment in their ability to achieve the nest complexity exhibited by the controls
  (MGI Ref ID J:130259)
  • at 1, 24 and 48 hours after introduction of new nestlet material, mice utilize significantly less material than wild-type controls
  (MGI Ref ID J:130259)
  • location of nest construction is different
  (MGI Ref ID J:130259)

• abnormal response to novel object
  • decreased amount of time spent investigating a novel object compared to wild-type
  (MGI Ref ID J:130259)
  • increased time until first contact with a novel object compared to wild-type
  (MGI Ref ID J:130259)

• abnormal social/conspecific interaction
  • fail to show a significant preference for spending time in the interaction chamber adjacent to the stimulus cage containing an unfamiliar mouse as opposed to spending time in the interaction chamber adjacent to an empty stimulus cage
  (MGI Ref ID J:130259)
  • mice fail to exhibit a preference for interacting with a new mouse over a familiar mouse
  (MGI Ref ID J:130259)

• abnormal behavior
  • frequently seen sleeping away from nesting material
  (MGI Ref ID J:130259)

• circling
  (MGI Ref ID J:130259)

• decreased vertical activity
  • the mean duration of each rearing event is decreased compared to controls
  (MGI Ref ID J:130259)
  • total number of rearings differs from wild-type littermates and C57BL/6J mice but not from 129X1/SvJ mice
  (MGI Ref ID J:130259)

• hyperactivity
  • a higher number of entries, in regards to the total transitions between all chambers, of a social interaction apparatus
  (MGI Ref ID J:130259)
  • a higher degree of ambulatory activity than control mice
  (MGI Ref ID J:130259)

craniofacial phenotype

• cleft palate
  • about 57% exhibit cleft palate
  (MGI Ref ID J:39801)

digestive/alimentary phenotype

• cleft palate
  • about 57% exhibit cleft palate
  (MGI Ref ID J:39801)

growth/size/body region phenotype

• cleft palate
  • about 57% exhibit cleft palate
  (MGI Ref ID J:39801)

• decreased body size
  • 5-10% that survive to adulthood are runted until weaning but achieve normal body weight by adulthood
  (MGI Ref ID J:39801)

hearing/vestibular/ear phenotype

• abnormal distortion product otoacoustic emission
  • at 16 kHz (middle cochlear region), ABR shifts are similar in magnitude to the observed DPOAE shifts, suggesting that the threshold shift arises at, or before, the stage of OHC transduction and amplification
  (MGI Ref ID J:112951)
  • at 6 weeks, homozygotes display significantly elevated DPOAE thresholds across all test frequencies relative to wild-type mice, with DPOAE thresholds of >60 dB at high frequencies
  (MGI Ref ID J:112951)

• increased or absent threshold for auditory brainstem response
  • ABR threshold elevation corresponds to >2 orders of magnitude of stimulus amplitude
  (MGI Ref ID J:112951)
  • at 6 weeks, homozygotes display severe cochlear dysfunction, as shown by highly significant ABR threshold elevations of 20-45 dB across a range of test frequencies, with peak loss occurring at 22.6 kHz
  (MGI Ref ID J:112951)

• sensorineural hearing loss
  (MGI Ref ID J:112951)

• abnormal auditory brainstem response waveform shape
  • at 6 weeks, suprathreshold ABR amplitudes in homozygotes are significantly reduced in amplitude, by at least 50% at all test frequencies and sound levels
  (MGI Ref ID J:112951)

• cochlear inner hair cell degeneration
  • at ~24 weeks, homozygotes display a nearly complete loss of IHCs throughout the basal 15% of the cochlear spiral, i.e., from 40 to 90 kHz according to the mouse cochlear frequency map
  (MGI Ref ID J:112951)

• abnormal cochlear IHC afferent innervation pattern
  • at >24 weeks, homozygotes display a significant reduction in the density of IHC afferent innervation relative to age-matched wild-type mice, indicating neuropathy
  (MGI Ref ID J:112951)

• abnormal cochlear OHC efferent innervation pattern
  • at >24 weeks, homozygotes display a reduction in OHC efferent innervation, with fewer efferent axons crossing to OHCs at the level of the tunnel of Corti relative to age-matched wild-type mice
  (MGI Ref ID J:112951)

• type IV spiral ligament fibrocyte degeneration
  • at >24 weeks, homozygotes display widespread loss of type IV fibrocytes, spreading farther apically
  (MGI Ref ID J:112951)

• abnormal cochlea morphology
  • rarity and fragility of homozygotes prevented evaluation of cochlear histopathology at 6 weeks, as none were killed at this age
  (MGI Ref ID J:112951)
  • at >24 weeks, homozygotes exhibit basal-turn histopathology
  (MGI Ref ID J:112951)

• cochlear outer hair cell degeneration
  • at ~24 weeks, homozygotes display a nearly complete loss of OHCs throughout the basal 15% of the cochlear spiral, i.e., from 40 to 90 kHz according to the mouse cochlear frequency map
  (MGI Ref ID J:112951)

mortality/aging

• perinatal lethality, incomplete penetrance
  • 90% die within 1 day of birth
  (MGI Ref ID J:39801)
  • 30% with normal palates die neonatally
  (MGI Ref ID J:39801)

• premature death
  • animals surviving to birth live an average of 18 weeks
  (MGI Ref ID J:39801)

nervous system phenotype

• cochlear ganglion degeneration
  • at >24 weeks, homozygotes show partial loss of spiral ganglion cells but only in cochlear regions in which IHCs are degenerated
  (MGI Ref ID J:112951)

• seizures
  • variable severity of epileptic seizures in mice over 10 weeks of age
  (MGI Ref ID J:39801)

• abnormal cochlear IHC afferent innervation pattern
  • at >24 weeks, homozygotes display a significant reduction in the density of IHC afferent innervation relative to age-matched wild-type mice, indicating neuropathy
  (MGI Ref ID J:112951)

• cochlear inner hair cell degeneration
  • at ~24 weeks, homozygotes display a nearly complete loss of IHCs throughout the basal 15% of the cochlear spiral, i.e., from 40 to 90 kHz according to the mouse cochlear frequency map
  (MGI Ref ID J:112951)

• small cochlear ganglion
  • adult homozygotes display significantly smaller cochlear ganglion cell areas at every sampled region in the spiral ganglion, except the apical cochlear turn
  (MGI Ref ID J:108890)
  • Normal - in contrast, mutant calretinin-positive ganglion cells are of normal size and proportion relative to wild-type cells
  (MGI Ref ID J:108890)
  • mutant calretinin-negative cells are smaller at each sampled location in the spiral ganglion relative to wild-type cells
  (MGI Ref ID J:108890)
  • the reduction in mean somatic area of mutant calretinin-negative cells is 5.2% in the basal turn, 8.7% in the middle turn, and 12.2% in the apical turn of the spiral ganglion relative to wild-type cells
  (MGI Ref ID J:108890)

• small vestibular ganglion
  • Normal - in contrast, mutant calretinin-positive ganglion cells are of normal size and proportion relative to wild-type cells
  (MGI Ref ID J:108890)
  • the reduction in mean somatic area of mutant calretinin-negative cells is 9.5% in the inferior division and 21.5% in the superior division of Scarpa's ganglion
  (MGI Ref ID J:108890)
  • adult homozygotes display significantly smaller ganglion cell areas in both divisions of Scarpa's ganglion (superior and inferior) relative to wild-type mice
  (MGI Ref ID J:108890)
  • mutant calretinin-negative cells are smaller in both divisions of Scarpa's ganglion relative to wild-type cells
  (MGI Ref ID J:108890)

• vestibular ganglion hypoplasia
  • Scarpa ganglion cell hypoplasia is strictly due to a size reduction of calretinin-negative ganglion cells
  (MGI Ref ID J:108890)
  • adult homozygotes show ganglion cell hypoplasia in both divisions of Scarpa's ganglion
  (MGI Ref ID J:108890)

• abnormal CNS synaptic transmission
  • 80% decrease in the maximal amplitude of GABA-activated chloride currents in dorsal root ganglion
  (MGI Ref ID J:39801)

• abnormal cochlear nerve morphology
  • at >24 weeks, homozygotes display clear signs of cochlear nerve abnormalities (progressive loss of afferent terminals)
  (MGI Ref ID J:112951)

• cochlear ganglion hypoplasia
  • adult homozygotes show hypoplasia of spiral ganglion cells in the middle and basal turns of the cochlea, while the apical turn remains unaffected
  (MGI Ref ID J:108890)
  • spiral ganglion cell hypoplasia is strictly due to a size reduction of calretinin-negative ganglion cells
  (MGI Ref ID J:108890)

• abnormal cochlear OHC efferent innervation pattern
  • at >24 weeks, homozygotes display a reduction in OHC efferent innervation, with fewer efferent axons crossing to OHCs at the level of the tunnel of Corti relative to age-matched wild-type mice
  (MGI Ref ID J:112951)

• cochlear outer hair cell degeneration
  • at ~24 weeks, homozygotes display a nearly complete loss of OHCs throughout the basal 15% of the cochlear spiral, i.e., from 40 to 90 kHz according to the mouse cochlear frequency map
  (MGI Ref ID J:112951)

skeleton phenotype

• type IV spiral ligament fibrocyte degeneration
  • at >24 weeks, homozygotes display widespread loss of type IV fibrocytes, spreading farther apically
  (MGI Ref ID J:112951)

behavior/neurological phenotype

• impaired coordination
  • have difficulty walking on grids and repeatedly fall off platforms and rotarods
  (MGI Ref ID J:39801)

• abnormal motor capabilities/coordination/movement
  (MGI Ref ID J:39801)

• abnormal parental behavior
  • failure to nuture offspring
  (MGI Ref ID J:39801)

• circling
  (MGI Ref ID J:108890)
  • many have been observed to run continuously in tight circles for extended periods of time
  (MGI Ref ID J:39801)

• seizures
  • variable severity of epileptic seizures in mice over 10 weeks of age
  (MGI Ref ID J:39801)

• hyperresponsive
  • hyperresponsive to human contact and other sensory stimuli
  (MGI Ref ID J:39801)

• impaired swimming
  • have difficulty swimming
  (MGI Ref ID J:39801)

• limb grasping
  (MGI Ref ID J:39801)

• hyperactivity
  (MGI Ref ID J:39801)