Fig. 7

A 303 kb deletion on chr18 affects semicircular canals and results in profound deafness. a Mean ABR thresholds of mice homozygous (n = 6, red triangles), heterozygous (n = 7, blue circles) and wildtype (n = 2, black inverted triangles) for the rthm allele (MFFD colony) at P28 ± 1 day. Error bars are standard deviations. See Additional File 1: Fig. S9c for individual thresholds. b Slc12a2 qPCR on RNA from the brains of P28 affected (n = 4, red, right) and unaffected (n = 4, green, left) mice. There is no significant difference between wildtypes and homozygotes (p = 1, Wilcoxon rank sum test). The bars show the mean expression level, and the points show the individual measures. Error bars are standard deviations. c Schematic showing the genes affected by the deletion. There are two protein-coding genes (black), one miRNA gene (orange), one snRNA gene (pink) and four lncRNA genes (blue). Slc12a2 is located 138 kb downstream of the 3’ end of the deletion (indicated by arrow top right). d Inner ears from affected (n = 3) and unaffected (n = 3) mice at P28 ± 1 day. The middle ear side, with the round (RW) and oval (OW) windows is shown on the left of each panel, and the brain side, where the cochlear nerve exits (CN), on the right. The round and oval windows and the cochlear nerve exits are marked by dotted lines, and the semicircular canals by dashed lines. Brackets indicate the cochlea (Co) and vestibular region (Ve). LSC = lateral semicircular canal; SSC = superior semicircular canal; PSC = posterior semicircular canal. Scale bar = 1 mm.The superior semicircular canals are thinner in affected mice (red arrowheads). e Immunohistochemistry of the cochlear duct of affected (n = 3) and unaffected (n = 3) mice at P28. Brown indicates the presence of MYO7A, which marks hair cells and the intermediate cells of the stria vascularis (marked by twin open arrowheads). Hair cells are only clearly visible in the unaffected mouse, indicated by the arrowheads (red for the inner hair cell and black for the outer hair cells). Asterisks show the Reissner’s membrane, which is displaced in affected mice. The top two panels show the apical region, 72% of the distance from the base to the apex. The lower panel shows the basal region, at 16% of the base-apex distance. Scale bar = 100 mm. Data underlying plots in this figure are in Additional File 3