This model of model of human autosomal recessive nonsyndromic deafness (DFNB12) has proven valuable in the assessment of otoprotective drug therapies.
The Jackson Laboratory cannot guarantee that cryorecovery of strains from the discontinued NIH-funded Neuroscience Mutagenesis Facility (NMF) will be successful or that the anticipated phenotype or genotype will be obtained. The cryorecovery fee for this effort will not be refunded or prorated if the recovery is unsuccessful or is in any way unsatisfactory. Genotyping will be the responsibility of the Purchaser.Read More +
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.
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 Name||12 Jackson|
|Allele Type||Chemically induced (ENU)|
|Allele Synonym(s)||Cdh23erl; Cdh23nmf308; erl; erlong; NMF308|
|Gene Symbol and Name||Cdh23, cadherin 23 (otocadherin)|
|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).|