Fig. 6: AAV-GRE-hsGJB2 rescues hearing in the Gjb2^Gjb6– mouse model of DFNB1.

a At P30, untreated Gjb2^Gjb6+ control mice (blue, n = 12) displayed normal hearing, while untreated Gjb2^Gjb6– mice (black, n = 9) were profoundly deaf. Hearing function was also evaluated in Gjb2^Gjb6– mice treated with AAV-GRE-hsGJB2.HA (n = 18). Auditory brainstem responses (ABRs) were measured in response to broadband clicks and tone bursts (left), along with distortion product otoacoustic emissions (DPOAEs) (right). Gjb2^Gjb6– mice injected with AAV-GRE-hsGJB2.HA showed no improvement in hearing. b Control mice injected with AAV-GRE-hsGJB2.HA displayed ABR responses comparable to untreated control mice (n = 6). However, their DPOAE levels were elevated. c At P30, Gjb2^Gjb6– mice treated with a high dose (1.4 × 10¹¹ vg, n = 7), medium dose (7.0 × 10¹⁰ vg, n = 16), or low dose (3.0 × 10¹⁰ vg, n = 21) of AAV-GRE-hsGJB2 demonstrated full preservation of click-evoked and tone-burst ABR responses, matching the levels observed in untreated control mice. d The amplitude of ABR wave 1 (measured from P1 to N1) evoked by a 16 kHz tone in treated mice at P30. e Average ABR waveforms from control untreated mice and Gjb2^Gjb6– mice treated with high, medium, and low doses. f Hearing recovery persisted through P90 in mice treated with high (n = 5) and medium doses (n = 7), maintaining ABR responses equivalent to those of normal-hearing controls (n = 6). Mice injected with a low dose (n = 10) exhibited elevated thresholds at P60. g The amplitude of ABR wave 1 in treated mice with high (n = 5), medium (n = 7), and low (n = 9) doses at P60 and P90. h DPOAE measurements at P30 in Gjb2^Gjb6– mice treated at P1 with AAV-GRE-hsGJB2 demonstrated robust rescue with all doses of AAV-GRE-hsGJB2. This rescue persisted at P60 and P90 with DPOAE levels comparable to those of normal hearing mice for high and medium doses. All data are presented as mean values  ±  SEM. Source data are provided as a Source Data file.