Figure 8. Intracochlear AAV2/8-mediated delivery of clarin-1 in Clrn1^ex4–/– mice leads to moderate hearing preservation.

(A) The schematic diagram (top panel) shows the AAV2/8-Clrn1-IRES-GFP vector used for gene delivery to the cochlea on P2–P3. The histogram indicates the percentage of GFP-labeled IHCs and OHCs on P20–P30 in Clrn1^ex4–/– mice. (B) Injections of either AAV2/8-Clrn1-IRES-GFP or AAV2/8-GFP had no effect on click ABR thresholds in WT mice. Injections of AAV2/8-GFP also had no impact on ABR thresholds in Clrn1^ex4fl/fl Myo15-Cre^+/– mice (unpaired Student’s t test). (C) ABR thresholds (mean ± SEM) in treated (purple, n = 9) and untreated (blue, n = 9) inner ears of P22–P24 Clrn1^ex4–/– and control (black, n = 5) mice. A decrease of about 10–15 dB in ABR thresholds relative to untreated ears was observed in Clrn1^ex4–/– ears after injection. **P < 0.01 (unpaired Student’s t test). (D) Early postnatal AAV2/8-mediated delivery of clarin-1 into Clrn1^ex4–/– ears did not prevent or correct the misshaping of the hair bundles. Both IHC and OHC hair bundles presented alterations in shape and a loss of short-row stereocilia due to the embryonic loss of clarin-1 (representative of 8 mice between P25 and P30). Scale bars: 1 μm.