C57BL/6J-Cdh23^12J/J

Stock number: 005462
Product name: neuroscience mutagenesis facility, 308
Research areas: Sensorineural Research

Description

This model of model of human autosomal recessive nonsyndromic deafness (DFNB12) has proven valuable in the assessment of otoprotective drug therapies.

Detailed description

Mice homozygous for this allele develop progressive hearing loss due to cochlear hair cell degeneration, but they do not display a vestibular defect. Auditory brainstem response has shown deficits as early as 26 days of age and complete deafness by approximately 3 months of age, a useful window of time for assessing otoprotective intervention. Stereocilia deformities have been found, particularly at the tip, with the loss of tip links. Hair cell degeneration initiates near the base of the cochlea, and spreads toward the apical turn with nearly complete loss of outer hair cells by 3 months of age. Inner hair cell loss is found at 5 months of age and loss of spiral ganglion cells has also been found after 5 months of age. Hair cell loss involves an apoptotic mechanism and anti-apoptotic inhibition has been shown to reduce hearing loss.

Development

The nmf308 mutation was identified in the progeny of an ENU mutagenized male as part of the Neuroscience Mutagenesis Program at The Jackson Laboratory. This mutation was subsequently identified as the twelfth mutation in the Cdh23 gene to arise at The Jackson Laboratory. Mice were maintained coisogenic on the C57BL/6J background and embryos were generated for cryopreserved by in vitro fertilization of C57BL/6J oocytes with sperm from homozygous males.

Allele

Symbol: Cdh23^12J
Name: 12 Jackson
MGI accession ID: MGI:4453135
Generation method: Chemically induced (ENU)
Synonyms: Cdh23^erl; Cdh23^nmf308; erl; erlong; NMF308
Marker symbol: Cdh23
Marker name: cadherin 23 (otocadherin)
Marker synonyms: 4930542A03Rik; ahl; bob; CDHR23; mdfw; nmf112; nmf181; nmf252; PITA5; sals; USH1D
Chromosome: 10
Strain of origin: C57BL/6J
Molecular note: This ENU-induced mutation is a T to C transition at coding nucleotide 208, which is base pair 63 in exon 3, that results in replacement of serine by proline at amino acid position 70 (p.S70P).