Fig. 8: Delivery of AAV-mini-PCDH15-V4 rescues mechanotransduction and the ABR in Pcdh15R245X/R245X mice.
From: Mini-PCDH15 gene therapy rescues hearing in a mouse model of Usher syndrome type 1F
a Representative confocal microscopy images of FM1-43 dye loading in inner hair cells (IHCs) and outer hair cells (OHCs) from the middle region of the cochlea at P6. Pcdh15R245X/+ mice (left), uninjected Pcdh15R245X/R245X (right). b FM1-43 dye loading in Pcdh15R245X/R245X knockout mice injected with AAV-mini-PCDH15-V4. Loading was restored in most hair cells. c Average percentage of IHCs and OHCs loaded with FM1-43; knockout mice injected with AAV-mini-PCDH15-V4 (red, n = 8), uninjected Pcdh15R245X/+ normal control mice (gray, n = 6). About 80% of knockout cells loaded after treatment. d Representative transduction currents measured at P10-P17 (top) in response to −175 to 1135-nm bundle deflections (bottom). A Pcdh15R245X/+ hearing control IHC (left); a Pcdh15R245X/R245X knockout IHC expressing mini-PCDH15-V4 (right). e Peak transduction currents at P10-P17 from Pcdh15R245X/+ controls (n = 6 cells) and Pcdh15R245X/R245X knockouts treated with AAV-mini-PCDH15-V4 (n = 9 cells). Cells from five separate Pcdh15R245X/+ cochleas and six separate Pcdh15R245X/R245X treated knockout cochleas were studied. f Normalized open probability as a function of stimulus probe displacement for Pcdh15R245X/+ controls (black, n = 6 cells) and treated Pcdh15R245X/R245X knockouts (red, n = 9 cells). g Average auditory brainstem response (ABR) thresholds as a function of frequency in P35 Pcdh15R245X/+ controls (blue, n = 10), uninjected knockout (black, n = 4) and knockout mice injected with AAV-mini-PCDH15-V4 mice (red, n = 5). h Representative ABR traces at P35 from controls, uninjected knockout mice, and treated knockout mice. SP summating potential. Scale bars: (a, b) 10 µm. All data are presented as mean values ± SEM. Source data are provided as a Source Data file.
