Cdh23-flox Mouse

Cdh23, encoding a calcium-dependent transmembrane glycoprotein, forms the upper part of tip-links in inner ear hair cells, which are crucial for mechano-electrical transduction (MET) [2]. The gene is composed of 69 exons, and its cytoplasmic tail interacts with other proteins like harmonin in the upper tip-link density (UTLD) [2]. This function is essential for the transformation of acoustical waves into neurological signals in the inner ear [4].

Genetically modified mutant mice lacking Cdh23 exon 68 have compromised tip-link stability, resulting in progressive and noise-induced hearing loss, indicating that exon 68 inclusion is critical for tip-link stability through regulating condensate formation of UTLD components [2]. In zebrafish, knockout of cdh23 gene leads to a significant decrease in the response to sound stimulation, and genes like atp1b2b and myof may affect hearing by regulating ATP production and purine metabolism in cooperation with cdh23 [3].

In conclusion, Cdh23 is vital for the stability of tip-links in inner ear hair cells and the mechano-electrical transduction process. Studies on gene-knockout models in mice and zebrafish have revealed its role in hearing-related biological processes. Mutations in Cdh23 are associated with a broad spectrum of hearing loss, from non-syndromic to syndromic, and from congenital to age-related, providing insights into the molecular mechanisms of hearing loss [1].