Analysis Tools
hearing/vestibular/ear
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• at 6-10 weeks, homozygotes display minimal cochlear histopathology, with little hair cell loss outside of the extreme cochlear base
• at >24 weeks, homozygotes exhibit basal-turn histopathology
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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 6 weeks, OHC efferent function is significantly reduced, as assessed by measuring DPOAE suppression caused by efferent-bundle shocks; reduction is noted at test frequencies at which efferent effects are normally largest (11-32 kHz)
• by 6 weeks, immunostaining for a cholinergic marker (VAT) and a GABAergic marker (GAD) indicates loss of OHC efferent terminals in all cochlear regions, consistent with a reduction in shock-evoked efferent effects observed at this age
• however, no changes in efferent terminal development are noted up to 3 weeks of age
• importantly, no significant loss of afferent terminals is noted at 24 weeks
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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 6-10 weeks, homozygotes show loss of type IV fibrocytes in the spiral ligament of the basal turn
• at >24 weeks, loss of type IV fibrocytes is extended farther apically than at 6 weeks of age
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• at >24 weeks, all homozygotes show limbic degeneration i.e. widespread loss of a small population of fibrocytes at a location where the spiral limbus meets the osseous spiral lamina
• however, no changes in the stria vascularis are obserevd
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• at 6 weeks, amplitudes of ABR suprathreshold responses (wave 1) of homozygotes are reduced by 25-50% relative to wild-type mice, even at the highest test stimulus levels
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• at 6 weeks, homozygotes display cochlear dysfunction, as shown by significant ABR threshold shifts increasing from <5 to 20-30 dB with increasing tone frequency
• at 24 weeks, cochlear dysfunction is exacerbated, as mean ABR threshold shifts are shown to peak at 45 dB for test frequencies in the middle of the cochlea (16 kHz)
• at 24 weeks, male homozygotes display significantly greater ABR threshold shifts than females; however, no sexual dimorphism is noted at 6 weeks
• at 24 weeks, ABR threshold shifts are significantly larger than the observed DPOAE shifts
• however, at 6 weeks, homozygotes show no significant differences in cochlear vulnerability to acoustic trauma (measured via ABRs and DPOAEs at 12 hrs after a 2-hr exposure to a 8-16 kHz noise band at 89 dB SPL) or in recovery from acoustic trauma at 7 days after overexposure relative to age-matched wild-type control mice
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• at 6 weeks, homozygotes display increasing DPOAE threshold shifts from low to high frequencies
• at 24 weeks, ABR threshold shifts are significantly larger than the observed DPOAE shifts
• however, at 6 weeks, ABR shifts at 16 kHz (middle cochlear region) are similar in magnitude to the observed DPOAE shifts, suggesting that the ongoing degeneration is a type of neuropathy
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nervous system
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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 6 weeks, OHC efferent function is significantly reduced, as assessed by measuring DPOAE suppression caused by efferent-bundle shocks; reduction is noted at test frequencies at which efferent effects are normally largest (11-32 kHz)
• by 6 weeks, immunostaining for a cholinergic marker (VAT) and a GABAergic marker (GAD) indicates loss of OHC efferent terminals in all cochlear regions, consistent with a reduction in shock-evoked efferent effects observed at this age
• however, no changes in efferent terminal development are noted up to 3 weeks of age
• importantly, no significant loss of afferent terminals is noted at 24 weeks
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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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skeleton
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• at 6-10 weeks, homozygotes show loss of type IV fibrocytes in the spiral ligament of the basal turn
• at >24 weeks, loss of type IV fibrocytes is extended farther apically than at 6 weeks of age
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