Abstract
BackgroundWaardenburg syndrome (WS) is the consequence of an inherited autosomal dominant mutation which causes the early degeneration of intermediate cells of cochlear stria vascularis (SV) and profound hearing loss. Patients with WS may also experience primary vestibular symptoms. Most of the current WS studies did not discuss the relationship between WS and abnormal vestibular function. Our study found that a spontaneous mutant pig showed profound hearing loss and depigmentation. MITF-M, a common gene mutation causes type WS which affect the development of the intermediate cell of SV, was then identified for animal modeling.ResultsIn this study, the degeneration of vestibular hair cells was found in pigs with MITF-M. The morphology of hair cells in vestibular organs of pigs was examined using electron microscopy from embryonic day E70 to postnatal two weeks. Significant hair cell loss in the mutant saccule was found in this study through E95 to P14. Conversely, there was no hair cell loss in either utricle or semi-circular canals.ConclusionsOur study suggested that MITF-M gene mutation only affects hair cells of the saccule, but has no effect on other vestibular organs. The study also indicated that the survival of cochlear and saccular hair cells was dependent on the potassium release from the cochlear SV, but hair cells of the utricle and semi-circular canals were independent on SV.
Highlights
Waardenburg syndrome (WS) is the consequence of an inherited autosomal dominant mutation which causes the early degeneration of intermediate cells of cochlear stria vascularis (SV) and profound hearing loss
This expression of microphthalmia-associated transcription factor-M (MITF-M) isoform resembled the typical phenotype of Waardenburg syndrome type II (WS2) in humans, which was featured by severe hearing loss, heterochromia iridis and white forelocks [6, 7]
Based on the reconstructed 3D models of inner ears, whole spatial structures of the cochlea, vestibule, and semicircular canals were found in the WT and albino pigs (Fig. 2c and d)
Summary
Waardenburg syndrome (WS) is the consequence of an inherited autosomal dominant mutation which causes the early degeneration of intermediate cells of cochlear stria vascularis (SV) and profound hearing loss. Animal models are important tools to study the mechanisms of vestibular hair cell degeneration and to evaluate their influence on vestibular function. Our previous work reported a phenotype of miniature pigs with deafness and depigmentation which was caused by a mutation in the region of the melanocyte-specific promoter of microphthalmia-associated transcription factor (MITF) gene [5]. This expression of MITF-M isoform resembled the typical phenotype of Waardenburg syndrome type II (WS2) in humans, which was featured by severe hearing loss, heterochromia iridis and white forelocks [6, 7]. Studies related to cochleosaccular degeneration discussed its influence in a variety of animal models (mouse [8],cats [9], dogs [10, 11], mink [12]) and human [13]
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