Analysis Tools
mortality/aging
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• 26% of homozygotes died following tonic convulsion
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behavior/neurological
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• from P21 to P27, 95% of homozygotes exhibited wild running (compared to 10% in wild-type) and 68% exhibited convulsions during the first 20 seconds of auditory stimulation, indicating susceptibility to audiogenic seizures
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nervous system
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• from P21 to P27, 95% of homozygotes exhibited wild running (compared to 10% in wild-type) and 68% exhibited convulsions during the first 20 seconds of auditory stimulation, indicating susceptibility to audiogenic seizures
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• homozygotes show a gradually increasing disorganization of hair bundles from the cochlear base to apex, starting from P4 at the base; however, a typical staircase pattern shaped by three rows of stereocilia is observed
• at P6, both usherin and vezatin are no longer present at the base of the hair bundle (as in wild-type mice) but remain in the kinocilium both in OHCs and IHCs
• at P6, whirlin is detected only in the apical end of stereocilia and supernumerary neural edge microvilli instead of both the base and apical end of stereocilia as observed in wild-type mice
• at P7, a dramatic increase in adenylate cyclase 6 labeling is detected in both OHC and IHC stereocilia, extending along the entire length of stereocilia instead of being restricted to the stereocilial base
• in addition, the long cadherin 23 class A isoforms are absent, with the N1 (extracellular) epitope detected at P0 but not at P6, while the Ela3 (both intracellular and extracellular) epitope is abnormally preserved until P17
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• at P6, ankle links are absent from both cochlear inner and outer hair cell stereociliary bundles
• in contrast, other lateral links are still present
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• at P6, IHCs exhibit asymmetrical instead of symmetrical arch-shaped hair bundles
• notably, peripheral microvilli at the neural edge side fail to regress in most IHCs, whereas these microvilli normally disappear before P6 in wild-type mice
• in addition, peripheral microvilli undergo a stereocilia-like maturation as they organize themselves in one or two rows, conferring a circular shape to the hair bundle, their stereocilia base becomes sharpened, and they exhibit an increased phalloidin labeling at P11, indicating a progressive increase of actin filament content
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• at P6, most OHCs display U-shaped or rounded hair bundles, instead of the expected V shape seen in wild-type mice
• occasionally, peripheral microvilli at the neural edge side fail to regress in OHCs, whereas these microvilli normally disappear before P6 in wild-type mice
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• at P7, mechanoelectrical transduction (MET) currents elicited by mechanical stimulations of the hair bundle in the stimulatory direction are impaired in OHCs, with a significant shift of the relative Po-displacement curve toward larger displacements and a decrease in the slope, indicating reduced sensitivity of the hair bundle to mechanical stimulation
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• at P7, MET currents evoked by displacements of the hair bundle toward the tallest stereocilia (i.e., in the excitatory direction) are decreased in OHCs but not in IHCs
• surprisingly, in both OHCs and IHCs, stimulation of the hair bundle in the opposite (inhibitory) direction results in significant MET transduction currents which are reversibly abolished with dihydrostreptomycin, an MET channel blocker
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hearing/vestibular/ear
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• homozygotes show a gradually increasing disorganization of hair bundles from the cochlear base to apex, starting from P4 at the base; however, a typical staircase pattern shaped by three rows of stereocilia is observed
• at P6, both usherin and vezatin are no longer present at the base of the hair bundle (as in wild-type mice) but remain in the kinocilium both in OHCs and IHCs
• at P6, whirlin is detected only in the apical end of stereocilia and supernumerary neural edge microvilli instead of both the base and apical end of stereocilia as observed in wild-type mice
• at P7, a dramatic increase in adenylate cyclase 6 labeling is detected in both OHC and IHC stereocilia, extending along the entire length of stereocilia instead of being restricted to the stereocilial base
• in addition, the long cadherin 23 class A isoforms are absent, with the N1 (extracellular) epitope detected at P0 but not at P6, while the Ela3 (both intracellular and extracellular) epitope is abnormally preserved until P17
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• at P6, ankle links are absent from both cochlear inner and outer hair cell stereociliary bundles
• in contrast, other lateral links are still present
|
|
• at P6, IHCs exhibit asymmetrical instead of symmetrical arch-shaped hair bundles
• notably, peripheral microvilli at the neural edge side fail to regress in most IHCs, whereas these microvilli normally disappear before P6 in wild-type mice
• in addition, peripheral microvilli undergo a stereocilia-like maturation as they organize themselves in one or two rows, conferring a circular shape to the hair bundle, their stereocilia base becomes sharpened, and they exhibit an increased phalloidin labeling at P11, indicating a progressive increase of actin filament content
|
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• at P6, most OHCs display U-shaped or rounded hair bundles, instead of the expected V shape seen in wild-type mice
• occasionally, peripheral microvilli at the neural edge side fail to regress in OHCs, whereas these microvilli normally disappear before P6 in wild-type mice
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• at P7, mechanoelectrical transduction (MET) currents elicited by mechanical stimulations of the hair bundle in the stimulatory direction are impaired in OHCs, with a significant shift of the relative Po-displacement curve toward larger displacements and a decrease in the slope, indicating reduced sensitivity of the hair bundle to mechanical stimulation
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• at P7, MET currents evoked by displacements of the hair bundle toward the tallest stereocilia (i.e., in the excitatory direction) are decreased in OHCs but not in IHCs
• surprisingly, in both OHCs and IHCs, stimulation of the hair bundle in the opposite (inhibitory) direction results in significant MET transduction currents which are reversibly abolished with dihydrostreptomycin, an MET channel blocker
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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:122415 | |
