The mouse Cdh23ahl allele drives early cochlear dysfunction and phenotypic heterogeneity before progressive hearing loss

The Cdh23ahl allele in C57BL/6N mice produces early, highly variable auditory dysfunction, with significant threshold elevations at 3642 kHz by 1-month and later lower-frequency involvement.

• Why it matters: Although Cdh23ahl is known for progressive hearing loss, its broader impact on phenotype expressivity and early cochlear biology is unclear, complicating interpretation of studies using common inbred strains.
• What they did: The authors compared C57BL/6N mice to a co-isogenic strain where Cdh23ahl was repaired by genome editing, measuring auditory thresholds, P14 mechanoelectrical transduction properties, and cochlear transcriptional state changes at P16 and P30.
• The result: At P14, inner hair cells show tonotopically distinct transduction alterations (reduced maximal currents apically, increased basally) before threshold shifts, and by P30 Cdh23ahl cochleae show increased inter-individual transcriptomic dispersion linked to variable high-frequency dysfunction.

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