Phenotypes associated with this allele

• Allele Symbol: Cdh23^12J
• Allele Name: 12 Jackson
• Allele ID: MGI:4453135
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cdh23^12J/Cdh23^12J	involves: C3H/HeJ * C57BL/6J	MGI:5822882
hm2	Cdh23^12J/Cdh23^12J	involves: C57BL/6J	MGI:5141009
ht3	Cdh23^12J/Cdh23^v-2J	involves: C57BL/6J	MGI:5822869

Genotype
MGI:5822882

hm1

• Allelic Composition: Cdh23^12J/Cdh23^12J
• Genetic Background: involves: C3H/HeJ * C57BL/6J

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

hearing/vestibular/ear

abnormal cochlear hair cell stereociliary bundle morphology ( J:183808 )

• disorganized or V-shaped stereocilia lacking a staircase pattern and missing the tip link are found by 28 days of age

abnormal cochlear hair bundle tip links morphology ( J:183808 )

• tip link loss by 21 days of age

abnormal outer hair cell stereociliary bundle morphology ( J:183808 )

decreased cochlear hair cell stereocilia number ( J:183808 )

cochlear hair cell degeneration ( J:183808 )

• although the cochlear turn region is normal at 2 weeks of age, by 1 month of age inner hair cell degeneration is found, at 2 months of age outer hair cell degeneration is found, and hair cell loss progresses base to apex

• at 2 months of age there is activated caspase in the outer hair cells at the basal turn

cochlear inner hair cell degeneration ( J:183808 )

• by 3 months of age approximately 75% of inner hair cells are lost from the extreme apex, but not the base of the cochlea

cochlear outer hair cell degeneration ( J:183808 )

• by 3 months of age nearly all outer hair cells are lost except for a few in the apical third of the cochlea

organ of Corti degeneration ( J:183808 )

increased or absent threshold for auditory brainstem response ( J:183808 )

• at 3 months of age there is hearing loss at a wide range of sound frequencies with ABR thresholds increased from 30 dB to 100 dB at frequencies over 8 kHz

abnormal distortion product otoacoustic emission ( J:183808 )

• relative to C57BL/6J controls homozygotes have hearing loss across a wide range of sound frequencies

deafness ( J:183808 )

nervous system

abnormal cochlear hair cell stereociliary bundle morphology ( J:183808 )

• disorganized or V-shaped stereocilia lacking a staircase pattern and missing the tip link are found by 28 days of age

abnormal cochlear hair bundle tip links morphology ( J:183808 )

• tip link loss by 21 days of age

abnormal outer hair cell stereociliary bundle morphology ( J:183808 )

decreased cochlear hair cell stereocilia number ( J:183808 )

cochlear hair cell degeneration ( J:183808 )

• although the cochlear turn region is normal at 2 weeks of age, by 1 month of age inner hair cell degeneration is found, at 2 months of age outer hair cell degeneration is found, and hair cell loss progresses base to apex

• at 2 months of age there is activated caspase in the outer hair cells at the basal turn

cochlear inner hair cell degeneration ( J:183808 )

• by 3 months of age approximately 75% of inner hair cells are lost from the extreme apex, but not the base of the cochlea

cochlear outer hair cell degeneration ( J:183808 )

• by 3 months of age nearly all outer hair cells are lost except for a few in the apical third of the cochlea

Genotype
MGI:5141009

hm2

• Allelic Composition: Cdh23^12J/Cdh23^12J
• Genetic Background: involves: C57BL/6J

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:174758 )

N • normal gait and swimming ability indicating absence of vestibular abnormalities

decreased cochlear inner hair cell number ( J:174758 )

• after 5 months of age

decreased cochlear outer hair cell number ( J:174758 )

• progressive OHC loss beginning around 3 months of age and moves from the cochlear base to the apex

• loss is evident in the midcochlear turns at P100

• treatment with an apoptosis inhibitor reduces OHC loss

abnormal cochlear outer hair cell physiology ( J:174758 )

• expression analysis indicates enhanced apoptosis in OHC

abnormal auditory brainstem response ( J:174758 )

• first detectable with high frequencies at P40

• treatment with an apoptosis inhibitor lowers ABR thresholds

abnormal distortion product otoacoustic emission ( J:174758 )

• lower amplitudes at 7 weeks of age compared to mice homozygous for Cdh23^ahl

• treatment with an apoptosis inhibitor increases amplitudes

absent distortion product otoacoustic emissions ( J:174758 )

• at 22 weeks of age, at all frequencies tested

impaired hearing ( J:174758 )

• develops by P27

deafness ( J:174758 )

• by P90

nervous system

decreased cochlear inner hair cell number ( J:174758 )

• after 5 months of age

decreased cochlear outer hair cell number ( J:174758 )

• progressive OHC loss beginning around 3 months of age and moves from the cochlear base to the apex

• loss is evident in the midcochlear turns at P100

• treatment with an apoptosis inhibitor reduces OHC loss

abnormal cochlear outer hair cell physiology ( J:174758 )

• expression analysis indicates enhanced apoptosis in OHC

behavior/neurological

behavior/neurological phenotype ( J:174758 )

N • normal gait and swimming ability indicating absence of vestibular abnormalities

absent pinna reflex ( J:174758 )

• at 20 weeks of age in response to a 20 kHz 90 dB sound pressure level tone burst

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal recessive nonsyndromic deafness 12		DOID:0110467	OMIM:601386	J:174758

Genotype
MGI:5822869

ht3

• Allelic Composition: Cdh23^12J/Cdh23^v-2J
• Genetic Background: involves: C57BL/6J

hearing/vestibular/ear

increased or absent threshold for auditory brainstem response ( J:183808 )

• at 23 days of age compound heterozgyotes have increased ABR thresholds, but no circling or vestibular phenotype