Phenotypes associated with this allele

• Allele Symbol: Gjb2^tm1Ugds
• Allele Name: targeted mutation 1, Unite de Genetique des Deficits Sensoriels
• Allele ID: MGI:2183509
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Gjb2^tm1Ugds/Gjb2^tm1Ugds Tg(Otog-cre)1Ugds/0	involves: 129P2/OlaHsd * C57BL/6	MGI:3588875
cn2	Gjb2^tm1Ugds/Gjb2^tm1Ugds Tg(Sox10-cre)1Wdr/0	involves: 129P2/OlaHsd * C57BL/6 * CBA	MGI:5571190
cn3	Gjb2^tm1Ugds/Gjb2^tm1Ugds Tg(Sox10-cre)1Wdr/0	involves: 129S2/SvPasCrl * C57BL/6 * CBA	MGI:5297177

Genotype
MGI:3588875

cn1

• Allelic Composition: Gjb2^tm1Ugds/Gjb2^tm1Ugds; Tg(Otog-cre)1Ugds/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

hearing/vestibular/ear

abnormal cochlear inner hair cell morphology ( J:77823 )

• direct efferent synapses are present on inner hair cells

abnormal inner hair cell synaptic ribbon morphology ( J:77823 )

• several synaptic ribbons, instead of the usual single one, are frequently observed in the active zone of the inner hair cell synaptic area

cochlear outer hair cell degeneration ( J:77823 )

• outer hair cells are damaged or lost

degeneration of organ of Corti supporting cells ( J:77823 )

• supporting cells of outer hair cells are damaged or lost

abnormal interdental cell morphology ( J:77823 )

• at P60, some interdental cells of the spiral limbus are missing

cochlear degeneration ( J:77823 )

• observe death of various cells in the cochlea that is not seen in wild-type

organ of Corti degeneration ( J:77823 )

• organ of Corti tends to collapse starting at P15-P16

• many epithelial cells have an altered shape and the reticular lamina is disrupted

abnormal cochlear endolymph ionic homeostasis ( J:77823 )

• decreased endolymphatic K⁺ concentration

decreased endocochlear potential ( J:77823 )

increased or absent threshold for auditory brainstem response ( J:77823 )

• 4 inner ears out of 41 had a hearing threshold > 100 dB sound pressure level (SPL)

sensorineural hearing loss ( J:77823 )

• at 3 to 12 weeks of age, mice showed a significant hearing loss, compared to heterozygous and control mice, for all frequencies tested; it ranged from 30 dB to more than 70 dB, with an average of 30 dB at 8 kHz, 31 dB at 16 kHz, and 36 dB at 32 kHz

• analysis of mutant mice individually showed that the hearing loss was more pronounced at 32 kHz than at 8 kHz

nervous system

abnormal cochlear inner hair cell morphology ( J:77823 )

• direct efferent synapses are present on inner hair cells

abnormal inner hair cell synaptic ribbon morphology ( J:77823 )

• several synaptic ribbons, instead of the usual single one, are frequently observed in the active zone of the inner hair cell synaptic area

cochlear outer hair cell degeneration ( J:77823 )

• outer hair cells are damaged or lost

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal recessive nonsyndromic deafness 1A		DOID:0110475	OMIM:220290	J:77823

Genotype
MGI:5571190

cn2

• Allelic Composition: Gjb2^tm1Ugds/Gjb2^tm1Ugds; Tg(Sox10-cre)1Wdr/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CBA

hearing/vestibular/ear

cochlear hair cell degeneration ( J:206835 )

• at 1 month of age, hair cells are partly degenerated and by 6 months, hair cells are absent

degeneration of organ of Corti supporting cells ( J:206835 )

• supporting cells in the auditory epithelium are seen in some areas but missing in others

organ of Corti degeneration ( J:206835 )

• cochleae display severe and rapid degeneration of the organ of Corti; degeneration is seen as early as 1 month of age and rapidly progresses from base to apex, such that by 6 months of age the auditory epithelium is flat throughout the cochlea

deafness ( J:206835 )

• mice show ABR threshold shifts at 12, 16, and 24 kHz, indicating substantial hearing loss

nervous system

cochlear hair cell degeneration ( J:206835 )

• at 1 month of age, hair cells are partly degenerated and by 6 months, hair cells are absent

cochlear ganglion degeneration ( J:206835 )

• spiral ganglion neuron degeneration that progresses from base to apex such that by 6 months of age, all cochlear turns show severe degeneration

• mice treated with an adenovirus expressing BDNF show preservation of the spiral ganglion neurons in the base region but does not rescue the organ of Corti degeneration

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal recessive nonsyndromic deafness 1A		DOID:0110475	OMIM:220290	J:206835

Genotype
MGI:5297177

cn3

• Allelic Composition: Gjb2^tm1Ugds/Gjb2^tm1Ugds; Tg(Sox10-cre)1Wdr/0
• Genetic Background: involves: 129S2/SvPasCrl * C57BL/6 * CBA

hearing/vestibular/ear

abnormal hair cell physiology ( J:178055 )

• cochlear cultures fail to propagate calcium signals or release ATP following photostimulation with caged IP3 unlike wild-type cultures

nervous system

abnormal hair cell physiology ( J:178055 )

• cochlear cultures fail to propagate calcium signals or release ATP following photostimulation with caged IP3 unlike wild-type cultures