Analysis Tools
reproductive system
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• homozygous matings produce reduced litter size
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hearing/vestibular/ear
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• areas beneath the sensory apparatus show reduced F-actin content in the outer hair cells (OHC) of the cochlea, with an overall reduction of about 10%; F-actin loss occurs in an about 1 um thick apical layer underneath OHC stereocilia
• the intercentriolar distance is increased in P2 OHCs
• basal body docking to the axoneme of the kinocilium is affected; in the more mature OHC1 and OHC2 cells, the pericentriolar material-to-kinocilium base distance is increased by about 25%
• newborn mice show disruption of the tight spatial correlation of the kinociliar base and the stereocilia bundle and the distance of the kinociliar base to the stereocilia bundle is increased
• in OHC3s, the distance between the kinociliar base to the stereocilia bundle is increased by almost 30%
• the pericentriolar material and the base of the stereocilia bundle tip are misaligned in all three OHC rows
• the disruption of the alignment of the pericentriolar material (i.e. the kinocilia base) with the stereocilia bundle occurs along the symmetry axis
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• kinocilium shows premature regression at P8 and P9
• fewer kinocilia-bearing OHC3s are seen in the cochlea during the critical time window of cochlear maturation prior to hearing onset (P8) and at P9, kinocilium retraction is even more severe, with all three OHCs rows of the apico-medial turn of the cochlea showing fewer remaining kinocilia
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• sensory arrays of OHCs are altered, with a broader range of orientation angles of OHC stereocilia bundles in cochlea of young adult mice that is 37%-69% larger than in wild-type mice
• OHCs show a general rotational distortion of stereocilia bundles toward the apical turn of the cochlea in contrast to wild-type which show rotations towards the basal turn
• OHC row 3 shows the severest early misrotations
• the ranges of stereocilia bundle deviations are already increased in the OHCs of P8 pups and stereocilia bundle orientations in all three OHC rows already shows a direct shift toward positive directions as in adult
• however, individual stereocilia in the bundles and bundles themselves do not show defects and OHC stereocilia bundles in P2 newborns are correctly located, orientated, and aligned after completion of embryonic development
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• OHC row 3 shows an increased frequency of gaps which reflect a lack of an entire OHC in adult, but not P2, mice
• a trend toward a loss of hair cells is seen for IHCs
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• auditory brainstem response (ABR) thresholds to tone burst stimulation are only mildly elevated, especially for low-frequency stimuli, such as 4 kHz
• however, general waveform of evoked responses in ABR measurements is unaffected, the latencies and amplitudes of the individual ABR are normal for click stimulation ranging from 10 to 80 dB, indicating that general sound detection is not strongly impaired but at low frequencies shows some defects
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• the intensities of distortion product otoacoustic emissions (DPOAEs) from adult (12-14 weeks) is lower over the entire frequency range, indicating defective cochlear amplification
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nervous system
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• areas beneath the sensory apparatus show reduced F-actin content in the outer hair cells (OHC) of the cochlea, with an overall reduction of about 10%; F-actin loss occurs in an about 1 um thick apical layer underneath OHC stereocilia
• the intercentriolar distance is increased in P2 OHCs
• basal body docking to the axoneme of the kinocilium is affected; in the more mature OHC1 and OHC2 cells, the pericentriolar material-to-kinocilium base distance is increased by about 25%
• newborn mice show disruption of the tight spatial correlation of the kinociliar base and the stereocilia bundle and the distance of the kinociliar base to the stereocilia bundle is increased
• in OHC3s, the distance between the kinociliar base to the stereocilia bundle is increased by almost 30%
• the pericentriolar material and the base of the stereocilia bundle tip are misaligned in all three OHC rows
• the disruption of the alignment of the pericentriolar material (i.e. the kinocilia base) with the stereocilia bundle occurs along the symmetry axis
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• kinocilium shows premature regression at P8 and P9
• fewer kinocilia-bearing OHC3s are seen in the cochlea during the critical time window of cochlear maturation prior to hearing onset (P8) and at P9, kinocilium retraction is even more severe, with all three OHCs rows of the apico-medial turn of the cochlea showing fewer remaining kinocilia
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• sensory arrays of OHCs are altered, with a broader range of orientation angles of OHC stereocilia bundles in cochlea of young adult mice that is 37%-69% larger than in wild-type mice
• OHCs show a general rotational distortion of stereocilia bundles toward the apical turn of the cochlea in contrast to wild-type which show rotations towards the basal turn
• OHC row 3 shows the severest early misrotations
• the ranges of stereocilia bundle deviations are already increased in the OHCs of P8 pups and stereocilia bundle orientations in all three OHC rows already shows a direct shift toward positive directions as in adult
• however, individual stereocilia in the bundles and bundles themselves do not show defects and OHC stereocilia bundles in P2 newborns are correctly located, orientated, and aligned after completion of embryonic development
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• OHC row 3 shows an increased frequency of gaps which reflect a lack of an entire OHC in adult, but not P2, mice
• a trend toward a loss of hair cells is seen for IHCs
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cellular
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• kinocilium shows premature regression at P8 and P9
• fewer kinocilia-bearing OHC3s are seen in the cochlea during the critical time window of cochlear maturation prior to hearing onset (P8) and at P9, kinocilium retraction is even more severe, with all three OHCs rows of the apico-medial turn of the cochlea showing fewer remaining kinocilia
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• about 80% of OHCs show a disorganized pericentriolar material in the cochlea
• P8 cochlea show increased volume of the pericentriolar scaffold, with it being more than doubled in all three OHC rows
• however, the centrioles encased by the pericentriolar material do not show defects
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embryo
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• embryos show no obvious defects in embryogenesis, in body laterality establishment or in neural tube closure, an no exencephaly is seen
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