Figure 1.
Hearing Profile (A) and middle ear bone dissections (B–C) of eeyore mice.
ABR thresholds of hearing (grey bars) and deaf (black bars) eeyore littermates at 4 (*p = 4.8×10−10) and 24 (**p = 1.2×10−10) weeks of age. The ossicles appear largely normal in deaf mice (C), comparable to normal morphology of the malleus, incus and stapes in normal hearing mice (B). M; manubrium of malleus, A; articulation surfaces of malleus and incus joint, T; tubercle, G; gonial angle, LI; attachment points of suspensory ligaments of incus, LP; lenticular process, C; capitulum of stapes, V; arched ventral crus, F; footplate. Scale bar: 1 mm.
Figure 2.
Haematoxylin and Eosin (H&E) staining of cochlea sections from 8 week old hearing (A–C) and 8–24 week deaf (D–L) mice at the apical, middle and basal levels.
Normal cochlear morphology shows an intact organ of Corti and the presence of a tunnel containing inner and outer hair cells and intact spiral ganglion and stria vascularis (B). Collapse of the tunnel of Corti is evident by 8 weeks at the basal level in deaf mice (arrow in F), and degeneration of the spiral ganglion is apparent at the basal level by 12 weeks of age (asterix in I). SG, spiral ganglion; OHC, outer hair cells; IHC, inner hair cells; OC, organ of Corti; BM, basilar membrane. Scale bar: 100 μM.
Figure 3.
Scanning electron micrographs of cochlear sensory epithelium from 12–14 week old hearing (A, E and I) and deaf (B–D, F–H, J–L) mice at the apical, middle and basal cochlear level.
OHC bundles are disorganised and misorientated at the middle and basal levels of the cochlea. Bundles are completely missing at the basal level at this age. IHC have an abnormal morphology, appearing ‘OHC-like’ in structure. OHC, outer hair cells; IHC, inner hair cells. Scale bar: 10 μM (A, B, E, F, I and J), 2 μM (C, D, G, H, K and L).
Figure 4.
SNP mapping of the mutation in eeyore mice.
DNA from 3 hearing (H) and 8 of 16 deaf (D) mice were analysed for SNP markers on chromosome 18, which are listed in the first column and indicate megabase position (4.6–40.3 Mb). The mouse identification numbers and phenotypes are indicated at the top of each column. The genotype of each mouse is either homozygous for C57BL/6 (black) or BALB/c (white) or heterozygous (grey) for that marker. On the right is a diagram of mouse chromosome 18 showing the interval to which the deafness phenotype mapped to.
Table 1.
Top-ranked candidate genes in the eeyore genetic interval.