CIB2 isoforms and hearing sensitivity in CIB2−/− mice

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CIB2 isoforms and hearing sensitivity in CIB2−/− mice CIB2 isoforms and hearing sensitivity in CIB2−/− mice ADomain structure of the CIB2 protein, indicating the positions of the CIB2 mutations in USH1J (red) and DFNB48 (green) patients. The CIB2‐floxed mice, CIB2fl/fl, were engineered by adding LoxP sites on either side of exon 4, which is common to all four known CIB2 transcripts.BRT–PCR analysis confirming the loss of CIB2 exon 4‐containing transcripts in the inner ear, eye, brain, muscle, kidney and testis of CIB2−/− mice. β‐Actin was used as an endogenous control.C, DABR thresholds (C) and DPOAE amplitudes (D) in CIB2+/− (dark, n = 6) and CIB2−/− (red, n = 9) P20‐P25 mice. ABR thresholds in CIB2−/− mice exceeded 100 dB SPL (mean ± SD), indicating profound deafness. (D) DPOAE amplitudes were absent in CIB2−/− P20 mice at 10 and 15 kHz (red) (Mann–Whitney, ***P = 0.002 for both 10 and 15 kHz).EMET responses in OHCs from CIB2+/− and CIB2−/− P7 mice. The left panels show the mechanical stimulation protocol, with examples of MET currents for each genotype. In the right panels, the MET current values and mean amplitude‐displacement relationships (I(X)) (mean ± SD) in CIB2+/− (black, n = 3 cells) and CIB2−/− (red, n = 5) mice highlight the absence of a MET response in CIB2−/− OHCs (Welch's unpaired t‐test, ****P = 0.0007). Vincent Michel et al. EMBO Mol Med. 2017;9:1711-1731 © as stated in the article, figure or figure legend