Fig. 6

A deletion within the Pcdh15 gene causes disruption of stereocilia bundles and profound deafness. a Schematic of Pcdh15 isoforms showing the internal deletion in Pcdh15 (jigl, MEWY colony), showing the effects of the deletion on different transcripts (not to scale). Red indicates the deleted exons. Transcripts are shown in their entirety, but not all exons are visible due to scale. b Mean ABR thresholds of affected (n = 6, orange triangles) and unaffected (n = 7, teal circles) mice at P30. Error bars are standard deviations. c Scanning electron micrographs of the organ of Corti at P30 (60–70% of the distance from base to apex, scale bar = 10 µm, n = 3 unaffected, 6 affected mice) and P5 (50–80% of the distance from base to apex, scale bar = 10 µm, n = 5 unaffected, 4 affected mice). Mice at P5 were not able to be phenotyped by circling behaviour, but the scanning electron micrographs showed a clear bimodal distribution of affected and unaffected based on disorganisation of hair bundles, and we were unable to amplify the deleted region in affected pups (see Table S7 for primers). Representative examples are shown here. Affected P5 mice had less well-organised hair cell bundles than unaffected littermates. The overall “V” shape of the stereocilia bundle was distorted and irregular in the organ of Corti of affected mice. The polarity of some outer hair cell bundles was rotated by up to 90°, and in some cases, the kinocilium was on the opposite side of the cell (arrowhead in d). d Close ups of hair cells at P5, showing cochlear hair cells from the same region as in c, and vestibular hair cells from the macula (n = 2 unaffected and 2 affected mice). The arrowhead indicates an example of a kinocilium on the opposite side of the outer hair cell from the stereocilia bundle. Macular stereocilia bundles seemed to have a more ordered staircase structure in the mice classed as unaffected compared to affected mice, where all stereocilia appeared to be long with little sign of a staircase arrangement. Scale bars = 2 µm. Data underlying plots in this figure are in Additional File 3