All Phenotypes Slc26a5<tm1Jnz> MGI Mouse

short cochlear outer hair cells ( J:79029 , J:91680 )

• at 7-9 weeks, homozygotes exhibit a decrement in OHC lengths in all cochlear turns while hair bundle morphology on all three rows of OHCs is normal (J:79029)

• at P21 (when OHC loss is minimal but ABR thresholds are elevated), mutant OHCs display reduced cell length (J:91680)

• however, no ultrastructural abnormalities in sterocilla, lateral wall, tight junction or synapses are noted at P21 (J:91680)

cochlear hair cell degeneration ( J:91680 )

• only sporadic cochlear hair cell loss is noted at P21

• a striking increase in hair cell loss is observed between P28 and P42

• at all stages, % of hair cell decreases gradually from the basal turn to the middle turn of the cochlea

• apoptosis of hair cells begins at P28, as confirmed by TUNEL assays

• loss of cochlear IHCs lags behind that of OHCs

• no significant cochlear hair cell loss occurs prior to P28

cochlear inner hair cell degeneration ( J:79029 , J:91680 )

• at 7-9 weeks, homozygotes show a nearly complete loss of cochlear IHCs in the basal 25% of the cochlear spiral (J:79029)

• no IHC loss is noted at P7 (J:79029)

• homozygotes show no remarkable cochlear IHC loss prior to P35; however, 29.3% of IHC are lost in the basal-most cochlear turn by P42 (J:91680)

cochlear outer hair cell degeneration ( J:79029 , J:91680 )

• at 7-9 weeks, homozygotes a nearly complete loss of cochlear OHCs in the basal 25% of the cochlear spiral (J:79029)

• no OHC loss is noted at P7 (J:79029)

• in a basal-most 7% cochlear region, 1.6% of OHCs are lost at P21, 10.6% of OHCs are lost at P28, and 94% of OHCs are lost at P42 (J:91680)

• at P28, the innermost row of OHCs shows significantly more loss relative to the middle and outermost OHC rows in the basal-middle cochlear turns (J:91680)

• by P42, 47.1% of OHCs are lost in the basal-most cochlear turn (J:91680)

• the number of apoptotic OHCs is maximal at P28 and P35, consistent with OHC loss (J:91680)

• at P42, more apoptotic cells are detected in the basal turn than in the middle and apical turns of the cochlea (J:91680)

abnormal Claudius cell morphology ( J:91680 )

• at P21-P35, some apoptosis occurs in Claudius cells, esp. in the basal-middle cochlear turn

degeneration of organ of Corti supporting cells ( J:91680 )

• by P42, homozygotes show complete loss of supporting cells in the basal-middle turns

• apoptosis is noted in inner phalangeal cells and Deiters cells as well as in inner sulcus cells

organ of Corti degeneration ( J:91680 )

• at P14 and P21, the organ of Corti appears intact in the basal-middle cochlear turns, whereas OHC loss is noted at P28

• at P35, collapse of the organ of Corti and loss of three rows of OHCs are noted in the basal-middle turns; few remaining supporting cells are observed

• by P42, complete collapse of the organ of Corti and loss of hair cells and supporting cells are observed in the basal-middle turns

absent cochlear microphonics ( J:79029 )

• homozygotes display decay of the cochlear microphonic at the cessation of the tone burst, as expected for a passive system

• no disruption of mechano-electrical transduction is noted in cochlear OHCs

decreased cochlear microphonics ( J:105502 , J:124148 )

• at 30-58 days of age, homozygotes exhibit a significant reduction in cochlear microphonic (CM) at 16 kHz relative to wild-type or heterozygous mice (J:105502)

• in homozygotes, CM remains ~12 dB below that in wild-type mice even at the highest levels (J:105502)

• OHC forward transduction appears normal, as homozygotes have wild-type-like nonlinear responses including harmonic and intermodulation distortion, CM pseudotransducer functions, both summating potential polarities, as well as normal uptake of the dye AM1-43 via transducer channels (J:105502)

• at 1-2 months of age, distortion product cochlear microphonics (DPCM) amplitudes are significantly depressed, esp. at low stimulus levels (J:124148)

• homozygotes exhibiting measurable DPOAEs have larger DPCM than those for which DPOAEs are below the noise floor (J:124148)

• in addition, the horizontal shift in DPCM growth functions is smaller than the loss of gain measured via CAP or via DPOAEs (J:124148)

• DPCM at 2 f1-f2 is ~20 dB down from the primaries, at high SPLs, in both mutant and wildtype mice, and no differences in CM Lissajous patterns are observed (J:124148)

absent cochlear outer hair cell electromotility ( J:79029 )

• in response to voltage steps (-120-60 mV in 20-mV steps) in whole-cell, voltage clamp recordings, isolated homozygous mutant cochlear OHCs show absence of in vitro electromotility at all points tested

increased or absent threshold for auditory brainstem response ( J:79029 , J:91680 )

• at 6-8 weeks of age, ABR thresholds were 45 - 65 dB higher than those in wild-type mice, a decrease in sensitivity of two to three orders of magnitude (J:79029)

• as early as P14, homozygotes exhibit a significant increase in ABR auditory thresholds (~25 dB) relative to wild-type littermates (J:91680)

• at P21, high-frequency ABR auditory thresholds are elevated by ~50 dB (J:91680)

decreased cochlear nerve compound action potential ( J:105502 , J:124148 )

• at 30-58 days of age, homozygotes display CAP thresholds shifts in a frequency-dependent manner, with a gain change of ~45 dB at 5 kHz and of ~60 dB at 33 kHz (J:105502)

• CAP input-output functions indicate that the low-level segment is absent, and response magnitudes are reduced for the high-level segment, especially at 12 and 32 kHz (J:105502)

• CAP input-output functions at 6 kHz show near-normal magnitudes at high levels where minimal amplification is expected (J:105502)

• simultaneous masking curves for CAPs produced in response to a 12 kHz probe tone indicate absence of frequency selectivity (i.e. no tuning) in homozygotes (J:105502)

• at 1-2 months of age, homozygotes of the F3-F5 generation display significant increases in CAP thresholds relative to wild-type mice, ranging from ~35 dB at 3.2 kHz to ~55 dB at 16 kHz (J:124148)

• however, homozygotes with the highest CAP thresholds show no measurable ear canal distortions, even at the highest SPLs (J:124148)

abnormal distortion product otoacoustic emission ( J:79029 , J:124148 )

• at 6-8 weeks of age, the increased DPOAE threshold shifts (45 - 55 dB) were similar to those seen with ABR (J:79029)

• at 1-2 months of age, DPOAEs are only measurable in ~50% of homozygotes, with the strongest responses noted for f2 = 22.6 and 8.0 kHz, i.e. frequencies close to the regions of maximum sensitivity in these mutants (J:124148)

• homozygotes in which DPOAEs are measurable correspond to cases with the lowest CAP thresholds (J:124148)

• when present, DPOAE amplitudes are clearly lower than those in either wild-type or heterozygous mice, with a horizontal shift of ~50 dB, i.e. matching the observed CAP threshold shift (""loss of cochlear amplifier gain"") (J:124148)

• persistence of attenuated high-level DPOAEs indicates that OHC somatic motility is not required for their production (J:124148)

absent distortion product otoacoustic emissions ( J:124148 )

• distortion products in both CM and otoacoustic emissions disappear rapidly after death, suggesting that these DPOAEs are produced by "active" processes in OHC stereocilia

impaired hearing ( J:79029 )

• at 6-8 weeks, homozygotes exhibit a frequency-dependent reduction in cochlear sensitivity, ranging from ~40 dB at 5.6 kHz to >60 dB at 22.6 kHz, due to a loss of OHC electromotility

deafness ( J:91680 )

• P21 homozygotes exhibit significant hearing loss (25 to 50 dB SPL) prior to any substantial cochlear hair cell loss