Abstract
Age-related hearing loss (AHL) in common inbred mouse strains is a genetically complex quantitative trait. We found a synonymous single-nucleotide polymorphism in exon 7 of Cdh23 that shows significant association with AHL and the deafness modifier mdfw (modifer of deafwaddler). The hypomorphic Cdh23753A allele causes in-frame skipping of exon 7. Altered adhesion or reduced stability of CDH23 may confer susceptibility to AHL. Homozygosity at Cdh23753A or in combination with heterogeneous secondary factors is a primary determinant of AHL in mice.
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Acknowledgements
We thank R. Pellegrino, M. Irby, A. Calderon, A. Derr and J. Fiallos for technical assistance, K. Steel for the V/Le strain and C. Kubisch, N. Fischel-Ghodsian and D. Drayna for discussions and their comments on the manuscript.
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Noben-Trauth, K., Zheng, Q. & Johnson, K. Association of cadherin 23 with polygenic inheritance and genetic modification of sensorineural hearing loss. Nat Genet 35, 21–23 (2003). https://doi.org/10.1038/ng1226
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DOI: https://doi.org/10.1038/ng1226
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