Analysis Tools
mortality/aging
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• animals surviving to birth live an average of 18 weeks
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• 30% with normal palates die neonatally
• 90% die within 1 day of birth
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growth/size/body
cleft palate
(
J:39801
)
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• about 57% exhibit cleft palate
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• 5-10% that survive to adulthood are runted until weaning but achieve normal body weight by adulthood
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behavior/neurological
limb grasping
(
J:39801
)
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• have difficulty walking on grids and repeatedly fall off platforms and rotarods
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• have difficulty swimming
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hyperactivity
(
J:39801
)
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• many have been observed to run continuously in tight circles for extended periods of time
(J:39801)
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• hyperresponsive to human contact and other sensory stimuli
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• failure to nuture offspring
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hearing/vestibular/ear
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• at >24 weeks, homozygotes exhibit basal-turn histopathology
• rarity and fragility of homozygotes prevented evaluation of cochlear histopathology at 6 weeks, as none were killed at this age
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• at >24 weeks, homozygotes display a significant reduction in the density of IHC afferent innervation relative to age-matched wild-type mice, indicating neuropathy
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• 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
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• 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
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• 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
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• at >24 weeks, homozygotes display widespread loss of type IV fibrocytes, spreading farther apically
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• at 6 weeks, suprathreshold ABR amplitudes in homozygotes are significantly reduced in amplitude, by at least 50% at all test frequencies and sound levels
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• 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
• ABR threshold elevation corresponds to >2 orders of magnitude of stimulus amplitude
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• 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
• 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
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nervous system
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• at >24 weeks, homozygotes display a significant reduction in the density of IHC afferent innervation relative to age-matched wild-type mice, indicating neuropathy
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• 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
|
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• 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
|
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• 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
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• at >24 weeks, homozygotes show partial loss of spiral ganglion cells but only in cochlear regions in which IHCs are degenerated
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• mutant calretinin-negative cells are smaller at each sampled location in the spiral ganglion relative to wild-type cells
• 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
• adult homozygotes display significantly smaller cochlear ganglion cell areas at every sampled region in the spiral ganglion, except the apical cochlear turn
• in contrast, mutant calretinin-positive ganglion cells are of normal size and proportion relative to wild-type cells
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• adult homozygotes show hypoplasia of spiral ganglion cells in the middle and basal turns of the cochlea, while the apical turn remains unaffected
• spiral ganglion cell hypoplasia is strictly due to a size reduction of calretinin-negative ganglion cells
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• adult homozygotes display significantly smaller ganglion cell areas in both divisions of Scarpa's ganglion (superior and inferior) relative to wild-type mice
• mutant calretinin-negative cells are smaller in both divisions of Scarpa's ganglion relative to wild-type cells
• 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
• in contrast, mutant calretinin-positive ganglion cells are of normal size and proportion relative to wild-type cells
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• adult homozygotes show ganglion cell hypoplasia in both divisions of Scarpa's ganglion
• Scarpa ganglion cell hypoplasia is strictly due to a size reduction of calretinin-negative ganglion cells
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• at >24 weeks, homozygotes display clear signs of cochlear nerve abnormalities (progressive loss of afferent terminals)
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• 80% decrease in the maximal amplitude of GABA-activated chloride currents in dorsal root ganglion
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craniofacial
cleft palate
(
J:39801
)
|
• about 57% exhibit cleft palate
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digestive/alimentary system
cleft palate
(
J:39801
)
|
• about 57% exhibit cleft palate
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skeleton
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• at >24 weeks, homozygotes display widespread loss of type IV fibrocytes, spreading farther apically
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