(A) Schematic showing the use of AG (sisomicin combined with furosemide) or DT to damage the mature cochlea in WT and Pou4f3^DTR/+ mice. (B–D) Saline-treated mice containing a full complement of myosin 7a⁺ cochlear inner hair cells and outer hair cells. A loss of outer hair cells after AG treatment and of inner hair cells after DT treatment was observed. Some outer hair cell loss after DT treatment was observed. (E) Quantification revealed a significant decrease in hair cell numbers in both damage paradigms. (F and G) ABR thresholds were significantly higher in both the AG- and DT-treated animals as compared with controls. A significant threshold shift was also observed in the DPOAEs in AG-treated animals, but not in the animals treated with DT. (H) Schematic of transgenic mouse models and experimental timeline. Cochleae were damaged on P21, tamoxifen was given on P22, followed by EdU administration from P23 to P25, and the animals were sacrificed after ABR on P28. (I) qPCR showing a significant reduction of Ctnnb1 (exon3) mRNA expression but not of Ctnnb1 (exon 13) mRNA expression in cochleae from Fgfr3-iCre Ctnnb1^fl(ex3)/+ mice. (J–M) No EdU⁺Sox2⁺ supporting cells or myosin 7a⁺ hair cells were detected after AG treatment in any of the genotypes examined. A persistent loss of outer hair cells was seen in these cochleae, without any new Sox2⁺myosin 7a⁺ hair cells. (N–Q) There were no EdU⁺ hair cells or supporting cells after DT treatment or formation of new Sox2⁺myosin 7a⁺ hair cells in any of the mouse cohorts. (R and S) Quantification of hair cells in AG- and DT-treated cochleae showing no change in hair cell numbers among genotypes. Data represent the mean ± SD. *P < 0.05 and **P < 0.01, by 2-tailed Student’s t test or 1-way ANOVA with Holm-Sidak multiple comparisons test. n = 3–11. Scale bars: 20 μm.