Disease relevance of Cdh23

• We also show an additive effect of the Cdh23 locus in modulating the progression of hearing loss in backcross mice [1].
• Progressive hearing loss and increased susceptibility to noise-induced hearing loss in mice carrying a Cdh23 but not a Myo7a mutation [2].

High impact information on Cdh23

• 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) [3].
• The mouse Cdh23 locus is comprised of two 5'-untranslated exons and 69 coding exons; together they cover a genomic distance of at least 350 kb [4].
• We recently showed that cadherins also play important roles in the inner ear; mutations in cadherin 23 (Cdh23) disrupt stereocilia organization on hair cells leading to deafness and vestibular dysfunction in waltzer mice [4].
• Amino acid sequence alignments and secondary structure prediction suggest that Cdh23 ectodomains adopt a conformation similar to the classic cadherins [4].
• A Cdh23 transcript with a spliced exon 68 is the predominantly expressed isoform in the organ of Corti [4].

Biological context of Cdh23

• Cadherin 23 (Cdh23) and protocadherin 15 (Pcdh15), mapping within the 95% confidence interval of ahl5, bear nucleotide polymorphisms in coding exons, but these appear to be unrelated to the hearing phenotype [5].
• Haplotype analyses across the Cdh23 locus demonstrated the phylogenetic relationship between Black Swiss and common inbred strains [5].
• A point mutation in a cadherin gene, Cdh23, causes deafness in a novel mutant, Waltzer mouse niigata [6].
• In contrast, CBy/ CAST-dfw2J/+ heterozygotes expressing even a single copy of the CAST/Ei-derived mdfw allele (Mdfw) retain their normal hearing function [7].
• By linkage analysis, we localized this locus (mdfw) to Chromosome 10, between markers D10Mit127 and D10Mit185, within a 4.0 +/- 1.1 cM genetic interval [7].

Anatomical context of Cdh23

• In addition, Myo1c does not bind to stereocilia from mice whose hair cells lack Cdh23 protein despite the presence of PIP2 in the stereociliary membranes [8].
• In contrast, FLAG-tagged TMCy:p.Arg3175His and human TMCy:c.9625_9626insC forms were both localized to the plasma membrane in cultured cells, allowing prediction that USH1D-associated CDH23:p.Arg3175His and CDH23:c.9625_9626insC proteins could be transported to the plasma membrane in vivo [9].

Associations of Cdh23 with chemical compounds

• The findings suggest that changes in the alpha-amino-3-hydroxy-5-methyl-4-isoxazole glutamate receptor subunits and/or their binding proteins are part of the phenotype of ahl, and may reflect a role of the glutamate receptor pathway in the mechanism of ahl [10].

Physical interactions of Cdh23

• Here we describe the identification and characterization of a new allele of deaf waddler (dfw2J) and present evidence for a hearing susceptibility locus (mdfw) that interacts with dfw [7].

Other interactions of Cdh23

• Our results reveal an epistatic relationship between the mdfw and the dfw genes and provide a model system to study nonsyndromic hearing loss in mice [7].

References