Degeneration of saccular hair cells caused by MITF gene mutation

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.

SlitC-PlexinA1 mediates iterative inhibition for orderly passage of spinal commissural axons through the floor plate

“…During neural circuit formation, axons are thought to navigate series of intermediate targets or choice points until they reach their final destination ( Comer et al, 2019 ; Raper and Mason, 2010 ). This concept emerged from seminal studies of limb bud innervation in insects ( Bate, 1976 ; Bentley and Keshishian, 1982 ; Ho and Goodman, 1982 ; Palka et al, 1992 ) and has been generalized to all contexts of long-distance axon projections.…”

Viewing the current situation of pig model application in China’s medical field from the application and funding of NSFC

“…They also proposed that MITF-M mutant pigs could provide an important animal model for cochlear implantation and cell therapy of patients with congenital hereditary deafness. In vestibular research, Du et al. (2019) studied characteristics and function of vestibular hair cells in miniature pigs with MITF-M mutation.…”

Analysis of MC1R, MITF, TYR, TYRP1, and MLPH Genes Polymorphism in Four Rabbit Breeds with Different Coat Colors

“…Previous investigations found that MC1R c.280_285del6 was more frequently presented in black rabbits, c.304_333del30 was recessive red/yellow, and c.[124A;125_130del6] was connected with Japanese brindling coat color [ 6 , 7 , 30 ]. The MITF gene polymorphism is known to be associated with the black and white colors in mice [ 31 ], pigs [ 32 ], cattle [ 33 ], horses [ 34 ], chickens [ 35 ], ducks [ 36 ], llamas [ 37 ], and so on. In this study, three SNPs (g.232587A < G, g.232650C < G, g.232766A < T) were found in the TB, SG, and SW breeds, and polymorphism distribution of the g.232587A < G sites were significantly different between TBs and SGs ( p < 0.01).…”