Phenotypes Associated with This Genotype

Genotype
MGI:5575514

• Allelic Composition: Tg(CAG-Diap3)924Lesp/0
• Genetic Background: FVB/NJ-Tg(CAG-Diap3)924Lesp

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

The stereocilia of Tg(CAG-Diaph3)771Lesp/0 and Tg(CAG-Diap3)924Lesp/0 mice become progressively abnormal from 4 to 24 weeks of age

mortality/aging

premature death ( J:193237 )

hearing/vestibular/ear

abnormal inner hair cell stereociliary bundle morphology ( J:193237 )

• at 8 weeks of age, many stereocilia appear to collapse against their nearest neighbors, by 16 weeks, stereocilia are elongated and adhere to their neighbors, and at 24 weeks, stereocilia elongate even further and there are fewer stereocilia per inner hair cell

• stereocilia are thicker at the base than in the middle or tips

• the few remaining inner hair cell stereocilia are arranged in a single row rather than 3 rows

• outer hair cell stereocilia show loss of structural integrity, particularly those in the outermost row

decreased inner hair cell stereocilia number ( J:193237 )

• number of stereocilia per inner hair cell is reduced to approximately 5 compared to several dozen in wild-type mice at 24 weeks of age, with apparent fusion of the membrane surrounding them

abnormal inner hair cell synaptic ribbon morphology ( J:193237 )

• inner hair cell ribbon loss is first seen at 8 weeks, preceding the onset of hearing loss, with a 22% reduction at 24 weeks of age

increased or absent threshold for auditory brainstem response ( J:193237 )

• mice exhibit higher thresholds indicating that higher sound pressure levels are required to elicit a brainstem response

impaired hearing ( J:193237 )

• mice do not show hearing loss at 4 and 8 weeks at 12 and 24 kHz, but at 16 and 24 weeks, threshold differences of 35 and 50 dB are seen, indicating severe hearing loss

cardiovascular system

abnormal cardiovascular system morphology ( J:193237 )

• cardiac defects

nervous system

abnormal inner hair cell stereociliary bundle morphology ( J:193237 )

• stereocilia are thicker at the base than in the middle or tips

• at 8 weeks of age, many stereocilia appear to collapse against their nearest neighbors, by 16 weeks, stereocilia are elongated and adhere to their neighbors, and at 24 weeks, stereocilia elongate even further and there are fewer stereocilia per inner hair cell

• the few remaining inner hair cell stereocilia are arranged in a single row rather than 3 rows

• outer hair cell stereocilia show loss of structural integrity, particularly those in the outermost row

decreased inner hair cell stereocilia number ( J:193237 )

• number of stereocilia per inner hair cell is reduced to approximately 5 compared to several dozen in wild-type mice at 24 weeks of age, with apparent fusion of the membrane surrounding them

abnormal inner hair cell synaptic ribbon morphology ( J:193237 )

• inner hair cell ribbon loss is first seen at 8 weeks, preceding the onset of hearing loss, with a 22% reduction at 24 weeks of age

behavior/neurological

behavior/neurological phenotype ( J:193237 )

N • mice do not show circling behavior

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal dominant auditory neuropathy 1		DOID:0060690	OMIM:609129	J:193237