Phenotypes Associated with This Genotype

Genotype
MGI:3693211

hm2

• Allelic Composition: Sod1^tm1Cep/Sod1^tm1Cep
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * CD-1

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

hearing/vestibular/ear

cochlear hair cell degeneration ( J:57435 )

• at 2, 7, and 17-19 months, homozygotes show a significant increase in age-related baso-apical progression of hair cell (HC) loss relative to age-matched wild-type mice, with a greater loss of OHCs than IHCs within each age group

• at 17 months, homozygotes display a near-complete loss of both OHCs and IHCs whereas wild-type mice show massive OHC loss with largely intact IHCs

• HC loss is prominent at 17-19 months, with a high degree of variability among individual cochleas

cochlear inner hair cell degeneration ( J:57435 , J:118910 )

• at 2 months, homozygotes exhibit ~20-80% IHC loss in the basal 30% of the cochlea whereas wild-type mice show >20% IHC loss only in the basal-most 5% of the cochlea (J:57435)

• between 2-7 months, IHC loss reaches 100% in the extreme base for both wild-type and mutant mice; however, homozygotes show a significantly greater IHC in the region 30-80% of the distance from the apex (J:57435)

• at 13 months, homozygotes display significant IHC degeneration in the mid-base and hook region relative to wild-type mice, with no significant differences between hetero- and homozygous mutant mice (J:118910)

cochlear outer hair cell degeneration ( J:57435 , J:118910 )

• at 2 months, homozygotes exhibit 20-100% OHC loss in the basal half of the cochlea whereas wild-type mice show only 0-50% OHC loss in the basal half; a similar OHC loss of <20% is noted in the apical half for both genotypes (J:57435)

• at 7 months, OHC loss progresses to the apical half of the cochlea in mutant mice but remains confined to the basal half in wild-type mice (J:57435)

• at 17-19 months, homozygotes exhibit 70-100% OHC loss throughout the cochlea relative to ~30-80% in wild-type mice (J:57435)

• at 13 months, homozygotes display a significantly greater OHC degeneration in the mid-base and hook region relative to wild-type mice, with no significant differences between hetero- and homozygous mutant mice (J:118910)

• at 13 months, homozygotes show a less pronounced OHC loss in the apical half relative to wild-type or heterozygous mice (J:118910)

pillar cell degeneration ( J:57435 )

• at 2 months, some pillar cells are lost

organ of Corti degeneration ( J:118910 )

• at 13 months, the organ of Corti is severely degenerated

abnormal auditory brainstem response waveform shape ( J:118910 )

• in response to 4-kHz tine bursts from 90 to 40 dB peak SPL, even 13-mo-old homozygotes with minimal hair cell loss display poorly defined ABR peaks relative to age-matched wild-type mice with maximal hair cell loss

increased or absent threshold for auditory brainstem response ( J:56971 , J:118910 )

• prior to broad-band noise exposure (4.0-45.0 kHz at 110 dB SPL for 1 hr), 5-13-wk-old homozygotes display a minor elevation of ABR thresholds (0-7 dB) at all test frequencies tested relative to age-matched wild-type mice (J:56971)

• specifically, pre-exposed 5-13-wk-old homozygotes show an ABR threshold elevation of 6-7 dB at 5 and 10 kHz, but not at 20 or 40 kHz (J:56971)

• pre-exposed 5-13-wk-old homozygotes and wild-type mice show a similar elevation of ABR thresholds of ~20-50 dB at 40 kHz (J:56971)

• at 13 months, homozygotes display significantly elevated ABR thresholds at 8-, and 16- and 32-kHz relative to wild-type mice (J:118910)

increased susceptibility to age-related hearing loss ( J:118910 )

• at 13 months, homozygotes exhibit increased susceptibility to age-related hearing loss and cochlear hair cell loss relative to wild-type mice

increased susceptibility to noise-induced hearing loss ( J:56971 )

• at 1 day after broad-band noise exposure (4.0-45.0 kHz at 110 dB SPL for 1 hr), homozygotes show a significantly greater acute ABR threshold elevation of 8 dB at 20 kHz relative to wild-type mice

• at day 14 after noise-exposure, homozygotes exhibit a significantly greater permanent threshold shift (PTS) only at 5 kHz (14 dB) and 40 kHz (6 dB) relative to wild-type mice

• overall, acute noise-exposed homozygotes show an additional PTS of ~10 dB at all test frequencies relative to wild-type mice, based on 28-day threshold data

• at 28 days after noise exposure, average cochleograms show no correlation between hair cell loss and homozygosity for the targeted gene

nervous system

cochlear hair cell degeneration ( J:57435 )

• at 2, 7, and 17-19 months, homozygotes show a significant increase in age-related baso-apical progression of hair cell (HC) loss relative to age-matched wild-type mice, with a greater loss of OHCs than IHCs within each age group

• at 17 months, homozygotes display a near-complete loss of both OHCs and IHCs whereas wild-type mice show massive OHC loss with largely intact IHCs

• HC loss is prominent at 17-19 months, with a high degree of variability among individual cochleas

cochlear inner hair cell degeneration ( J:57435 , J:118910 )

• at 2 months, homozygotes exhibit ~20-80% IHC loss in the basal 30% of the cochlea whereas wild-type mice show >20% IHC loss only in the basal-most 5% of the cochlea (J:57435)

• between 2-7 months, IHC loss reaches 100% in the extreme base for both wild-type and mutant mice; however, homozygotes show a significantly greater IHC in the region 30-80% of the distance from the apex (J:57435)

• at 13 months, homozygotes display significant IHC degeneration in the mid-base and hook region relative to wild-type mice, with no significant differences between hetero- and homozygous mutant mice (J:118910)

cochlear outer hair cell degeneration ( J:57435 , J:118910 )

• at 2 months, homozygotes exhibit 20-100% OHC loss in the basal half of the cochlea whereas wild-type mice show only 0-50% OHC loss in the basal half; a similar OHC loss of <20% is noted in the apical half for both genotypes (J:57435)

• at 7 months, OHC loss progresses to the apical half of the cochlea in mutant mice but remains confined to the basal half in wild-type mice (J:57435)

• at 17-19 months, homozygotes exhibit 70-100% OHC loss throughout the cochlea relative to ~30-80% in wild-type mice (J:57435)

• at 13 months, homozygotes display a significantly greater OHC degeneration in the mid-base and hook region relative to wild-type mice, with no significant differences between hetero- and homozygous mutant mice (J:118910)

• at 13 months, homozygotes show a less pronounced OHC loss in the apical half relative to wild-type or heterozygous mice (J:118910)

cochlear ganglion degeneration ( J:118910 )

• at 13 months, homozygotes show a significantly greater loss of spiral ganglion cells than age-matched or 2-month-old wild-type mice, with a higher degree of degeneration observed in the base than in the apex

• unlike eighth nerve fiber survival, survival of spiral ganglion cells is not compromised by age

abnormal cochlear nerve morphology ( J:118910 )

• at 13 months of age, both homozygotes and wild-type mice display significantly fewer eighth nerve fibers than 2-month-old wild-type mice, with significantly greater loss in aged homozygotes than in aged wild-type mice

• similar to hair cell loss, eighth nerve fibers in the basal half are more vulnerable to aging and ROS-mediated damage than fibers in the apical half