Phenotypes Associated with This Genotype

Genotype
MGI:2669261

• Allelic Composition: Slc26a5^tm1Jnz/Slc26a5⁺
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

hearing/vestibular/ear

cochlear inner hair cell degeneration ( J:79029 )

• at 7-9 weeks, F2 heterozygotes show scattered loss of cochlear IHCs in the basal 25% of the cochlear spiral

• however, no IHC loss is noted at P7

abnormal cochlear outer hair cell morphology ( J:79029 )

• at 7-9 weeks, F2 heterozygotes exhibit intermediate OHC lengths in all cochlear turns relative to wild-type and homozygous mutant mice

• however, hair bundle morphology on all three rows of OHCs appears unaffected

cochlear outer hair cell degeneration ( J:79029 )

• at 7-9 weeks, F2 heterozygotes show scattered loss of cochlear OHCs in the basal 25% of the cochlear spiral

• however, no OHC loss is noted at P7

decreased 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, OHCs isolated from F2 generation heterozygotes show a 54% reduction in in vitro electromotility relative to wild-type OHCs

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

• at 6-8 weeks of age, ABR thresholds for responses originating from cochlear regions with all hair cells present (frequencies 22.6 kHz) are elevated by 1-8 dB (J:79029)

• at P21, heterozygotes exhibit a significant increase in high-frequency ABR auditory thresholds (~3.5 dB) relative to wild-type littermates (J:91680)

abnormal distortion product otoacoustic emission ( J:79029 , J:118929 )

• at 6-8 weeks of age, DPOAE-based thresholds are 3.1-6.4 dB higher than those in control mice, excluding the highest test frequencies, where OHC loss complicates interpretation (J:79029)

• DPOAEs are reduced in F2 but not in F3-F5 heterozygotes (J:118929)

impaired hearing ( J:79029 , J:118929 )

• at 6-8 weeks, F2 generation heterozygotes show a 6 dB loss of cochlear sensitivity, i.e. a ~2-fold increase in cochlear thresholds relative to wild-type mice, due to a 54% reduction in OHC electromotility (J:79029)

• in stark contrast to F2 heterozygotes, F3-F5 heterozygotes display normal CAP thresholds, CAP tuning curves and CM input-output functions, with no significant differences in non-linear capacitance or OHC electromotility relative to wild-type mice (J:118929)

• consistent with normal hearing data in F3-F5 heterozygotes, immunocytochemical and western blot analyses show that wild-type-like prestin protein expression is attained in adolescent heterozygotes prior to P33 (J:118929)

nervous system

cochlear inner hair cell degeneration ( J:79029 )

• at 7-9 weeks, F2 heterozygotes show scattered loss of cochlear IHCs in the basal 25% of the cochlear spiral

• however, no IHC loss is noted at P7

abnormal cochlear outer hair cell morphology ( J:79029 )

• at 7-9 weeks, F2 heterozygotes exhibit intermediate OHC lengths in all cochlear turns relative to wild-type and homozygous mutant mice

• however, hair bundle morphology on all three rows of OHCs appears unaffected

cochlear outer hair cell degeneration ( J:79029 )

• at 7-9 weeks, F2 heterozygotes show scattered loss of cochlear OHCs in the basal 25% of the cochlear spiral

• however, no OHC loss is noted at P7

decreased 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, OHCs isolated from F2 generation heterozygotes show a 54% reduction in in vitro electromotility relative to wild-type OHCs

growth/size/body

decreased body weight ( J:79029 )

• at 1 month, F2 heterozygotes are viable and behaviorally normal but display a ~5% reduction in body weight relative to wild-type littermates