Analysis Tools
hearing/vestibular/ear
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• at P10, TEM analysis of the cochlear duct showed incomplete and lumpy chromatin condensation in OHC nuclei, indicating early apoptotic changes
• at P10, mutant OHCs are found frequently in abnormal positions among Sox2-positive nuclei of Deiters cells
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• by P11, mutant OHCs occasionally show subtle defects in bundle polarity
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• by P11
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• by 3 months of age, most mutant cochlear IHCs and OHCs are missing, indicating that OHC loss is followed by IHC degeneration in adult mice
• in contrast, mutant vestibular hair cells appear unaffected
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• although intact at P30, mutant IHCs degenerate by 3 months of age
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• at P11, mutant OHCs display signs of degeneration, including ruffling of the apical cell membrane and fused stereocilia
• by P30, mutant OHCs are either partially or completely degenerated, whereas IHCs and spiral ganglion neurons remain unaffected
• OHCs start degenerating at ~P8 and are lost progressively along the cochlea in a mosaic pattern, rather than in a basal-to-apical gradient
• OHC degeneration is rescued in cochlear organotypic cultures in low K+ milieu, indicating that HC loss is triggered by extracellular factors
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• at P30, homozygotes show a small but significant decrease in the number of Deiters cells
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• by 3 months of age, homozygotes show degeneration of the entire organ of Corti
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• although normal at P10, the EP is ~17% lower than that in wild-type controls at P30
• however, the barrier properties of tight junctions in the stria vascularis appear intact at P30
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• at P18, homozygotes show increased ABR thresholds (62 +/- 4 dB SPL) relative to heterozygous (39 +/- 4 dB) or age-matched wild-type controls (42 +/- 5 dB)
• by P30, homozygotes are severely hearing impaired (ABR thresholds >80 dB), and, by P60, most of them are deaf (ABR thresholds >90 dB)
• analysis of ABRs elicited by pure tones between 4 and 32 kHz indicated that homozygotes are equally affected across tested frequencies
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• at 2 months of age, DPOAEs are absent at all frequencies tested (6-28 kHz), unlike in wild-type or heterozygous littermates
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• homozygotes display an early onset and rapidly progressive hearing loss with no gross anatomical defects in the vestibular end organs
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nervous system
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• at P10, TEM analysis of the cochlear duct showed incomplete and lumpy chromatin condensation in OHC nuclei, indicating early apoptotic changes
• at P10, mutant OHCs are found frequently in abnormal positions among Sox2-positive nuclei of Deiters cells
|
|
• by P11, mutant OHCs occasionally show subtle defects in bundle polarity
|
|
• by P11
|
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• by 3 months of age, most mutant cochlear IHCs and OHCs are missing, indicating that OHC loss is followed by IHC degeneration in adult mice
• in contrast, mutant vestibular hair cells appear unaffected
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• although intact at P30, mutant IHCs degenerate by 3 months of age
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• at P11, mutant OHCs display signs of degeneration, including ruffling of the apical cell membrane and fused stereocilia
• by P30, mutant OHCs are either partially or completely degenerated, whereas IHCs and spiral ganglion neurons remain unaffected
• OHCs start degenerating at ~P8 and are lost progressively along the cochlea in a mosaic pattern, rather than in a basal-to-apical gradient
• OHC degeneration is rescued in cochlear organotypic cultures in low K+ milieu, indicating that HC loss is triggered by extracellular factors
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• although intact at P30, peripheral axons and somata of mutant spiral ganglion neurons show widespread degeneration by 3 months of age
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behavior/neurological
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• homozygotes show no gross defects in neurological function or reflexes
• vestibular function is intact in open-field and swim tests
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