Analysis Tools
mortality/aging
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• without intervention audiogenic seizures frequently result in death as a result of respiratory distress
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behavior/neurological
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• a high intensity sound stimulus triggers audiogenic seizures that frequently continue to full tonic-clonic extension
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hearing/vestibular/ear
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• by P2, homozygotes exhibit a disorganized cochlear hair bundle morphology, which is more prominent at P4
• no further exacerbation of hair bundle morphology occurs with increasing age, as determined at P28
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• at P2, ankle links are absent from both cochlear inner and outer hair cell stereociliary bundles
• surprisingly, ankle links in mutant vestibular hair cell stereociliary bundles appear unaffected
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• at P2, many of the homozygous mutant OHC stereociliary bundles in apical coils display a less sharply defined V-shape relative to those in heterozygous OHCs
• by P4, mutant OHC stereociliary bundles display a more rounded shape and lack bilateral symmetry
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• by P4, mutant OHC stereociliary bundles exhibit a degree of disorientation
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• by 2 months, homozygotes exhibit significant IHC degeneration in the basal-most regions of the cochlea
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• by 2 months, homozygotes exhibit significant OHC degeneration in the basal half of the cochlea
• notably, loss of OHCs is prominent in the innermost row
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• by 2 months, homozygotes display loss of inner and outer pillar cells in the basal-most regions of the cochlea
• loss of pillar cells results in complete collapse of the end organ in the basal cochlear turn
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• by 2 months, homozygotes exhibit significant degeneration of the organ of Corti in the basal, high frequency cochlear turn
• at 2 months, the middle and apical turns are less affected, although they do exhibit a disarray of stereociliary bundles
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• single-cell recordings show that most cochlear OHCs fail to respond to fairly large hair bundle displacements by P7
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• FM1-43 dye loading expts indicate impaired mechanotransduction in both inner and outer cochlear hair cells
• 10 of 11 apical-coil OHCs obtained from homozygotes (aged P6-P8) exhibit absence of transduction currents with stimuli covering a wide range of bundle positions; the one transducing OHC had maximal currents of only 20 pA
• in contrast to cochlear hair cells, transduction currents obtained from vestibular (utricular) hair cells remain unaffected, consistent with a normal gait and balance behavior
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• at 3 weeks, homozygotes display elevated ABR thresholds by ~20 dB for responses to low frequency stimulation (2-2.8 kHz) and by ~60 dB for responses to higher frequency stimuli
• by 6 months, average threshold values are increased by ~10 dB for responses to higher frequency stimuli (>10 kHz), with values of 95-100 dB SPL regardless of stimulus frequency
• fewer 6-mo-old homozygotes are responseive to highest levels of stimulation (>105 dB SPL) at high frequencies (>10 kHz) relative to 3-wk-old homozygotes
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• at 2 months, homozygotes completely lack distortion product otoacoustic emissions (DPOAEs), indicating failure of OHC to amplify basilar membrane motion
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• ABRs indicate that homozygotes are profoundly deaf by 3 weeks of age
• acoustic sensitivity is progressively decreased over the following month
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vision/eye
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• at 15 months, the amplitudes of component waves of electroretinograms are reduced by 26-37% for all stimulus conditions in light-adapted cone-only responses
• however, no gross retinal abnormalities (i.e. retinitis pigmentosa) are detected by funduscopic or histological analyses
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• homozygotes exhibit age-related loss of visual function
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nervous system
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• a high intensity sound stimulus triggers audiogenic seizures that frequently continue to full tonic-clonic extension
|
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• by P2, homozygotes exhibit a disorganized cochlear hair bundle morphology, which is more prominent at P4
• no further exacerbation of hair bundle morphology occurs with increasing age, as determined at P28
|
|
• at P2, ankle links are absent from both cochlear inner and outer hair cell stereociliary bundles
• surprisingly, ankle links in mutant vestibular hair cell stereociliary bundles appear unaffected
|
|
• at P2, many of the homozygous mutant OHC stereociliary bundles in apical coils display a less sharply defined V-shape relative to those in heterozygous OHCs
• by P4, mutant OHC stereociliary bundles display a more rounded shape and lack bilateral symmetry
|
|
• by P4, mutant OHC stereociliary bundles exhibit a degree of disorientation
|
|
• by 2 months, homozygotes exhibit significant IHC degeneration in the basal-most regions of the cochlea
|
|
• by 2 months, homozygotes exhibit significant OHC degeneration in the basal half of the cochlea
• notably, loss of OHCs is prominent in the innermost row
|
|
• single-cell recordings show that most cochlear OHCs fail to respond to fairly large hair bundle displacements by P7
|
|
• FM1-43 dye loading expts indicate impaired mechanotransduction in both inner and outer cochlear hair cells
• 10 of 11 apical-coil OHCs obtained from homozygotes (aged P6-P8) exhibit absence of transduction currents with stimuli covering a wide range of bundle positions; the one transducing OHC had maximal currents of only 20 pA
• in contrast to cochlear hair cells, transduction currents obtained from vestibular (utricular) hair cells remain unaffected, consistent with a normal gait and balance behavior
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Usher syndrome type 2C | DOID:0110839 |
OMIM:605472 |
J:109595 | |
