Fig. 5

Clarin 2 is required for hearing function in mouse. a The genomic structure of mouse Clrn2 (ENSMUST00000053250), and domains of the encoded tetraspan-like glycoprotein (232 amino acids). The positions of the transmembrane (TM) domains (dark green) and the structures of the WT Clrn2 and Clrn2^del629 alleles are indicated. Deletion of exon 2 leads to a shortened clarin 2 lacking the two central transmembrane domains. b ABR threshold measurements at P21 (± 1 day) show that Clrn2^{del629/del629} mice (red) exhibit a severe-to-profound hearing loss affecting all frequencies tested, with thresholds at 80 dB SPL and beyond. Age-matched Clrn2^+/+ (black) and Clrn2^del629/+ (grey) controls display thresholds within the expected range (15–40 dB SPL). Averaged DPOAE responses at P28 (± 1 day), showing significantly reduced responses in Clrn2 ^{del629/del629} mice. Data shown are mean ± SD. **p < 0.001, one-way ANOVA. c Pseudo-colored scanning electron micrographs illustrate the three full rows, tallest (red), middle (blue) and short (yellow), of P28 (± 1 day) stereocilia in IHC and OHC hair bundles. Unlike the fragmented hair bundle in Clrn1^−/− mice, lack of clarin 2 does not affect the shape of IHC or OHC hair bundles. However, all the short row stereocilia have completely or partially regressed in the absence of either clarin protein. Scale bar = 1 µm