Figure 1.

Inner ear phenotype of hspn/hspn mutant mice. (A) Hearing assessment by ABR. Average ABR thresholds of +/hspn heterozygous control mice (N = 32) tested at 5–12 weeks of age compared with those of hspn/hspn mutants (N = 7) tested at 4–5 weeks of age. The +/hspn control mice exhibited normal thresholds at all test frequencies (8, 16, and 32 kHz), whereas the highly elevated ABR thresholds of hspn/hspn mutant mice indicated profound hearing impairment. Error bars represent SD. (B) Cleared whole mounts of inner ears from 4-week-old adult mice. Inner ears of the adult hspn/hspn mutant shows reduced development of the semicircular canals (sc) and a much wider and shorter cochlea (coch) than that of the +/+ control. Bar, 1 mm. (C) Paintfills of the membranous labyrinths of inner ears from E15.5 embryos. Compared with the normal morphology of +/+ controls, inner ears of hspn/hspn mutants lack an endolymphatic sac (es) and duct, have a severe reduction in semicircular canal development, and exhibit a swollen and shortened cochlear duct (cd). The saccule (s) and cochlear duct were present in all hspn/hspn mutant inner ears examined; however, the extent of dorsal structure development varied. Posterior semicircular canals (psc) and superior semicircular canals (ssc) never developed in mutant inner ears, but there was variable development of the lateral semicircular canal (lsc) and utricle (u). Bar, 0.5 mm. (D) SEM surface images of the organ of Corti in the midapical region of the cochlea from a 4-week-old hspn/hspn mutant mouse and an age-matched +/+ control. Although a single row of inner hair cells (IHCs) and three rows of outer hair cells (OHCs) are present in both mutant and control mice, the hair cells of hspn/hspn mutant mice are disorganized, with an extra row of OHCs near the cochlear apex. Bar, 20 μm.