αジストログリカン糖鎖不全型筋ジストロフィーは末梢蝸牛神経の髄鞘化障害による聴覚異常を合併する

抄録

Most of hearing loss (HL) is caused by problems in the cochlea; however, some are from problems in the cochlear nerve linking hair cells to the brain. The anatomical structure “glial dome” demarcates the peripheral and central segment of the cochlear nerve at the cochlear modiolus: the former is myelinated by Schwann cells and located at the Rosenthal’s canal (RC) and osseous spiral lamina (OSL). Muscular dystrophies (MDs) are characterized by progressive degeneration of skeletal muscle. MD-dystroglycanopathy (MD-DG) is caused by aberrant glycosylation of α-dystroglycan, and accompanied with various non-muscular symptoms. Since no comprehensive study regarding HL in MD-DG has accomplished, we investigated two mouse models of MD-DG, LARGE-deficient and POMGnT1-KO mice. MD-DG mice showed nonprogressive HL with delayed wave I latency in auditory brainstem response (ABR). Glycosylated α-dystroglycan is rich at the RC and OSL in controls, and decreased in MD-DG cochleae. Additionally, abnormal myelination of the peripheral cochlear nerve was observed at the RC and OSL by immunostaining, immunoblotting, electronic microscopy. Furthermore, Fukuyama congenital MD, a type of MD-DG, patients showed delayed wave I latency in ABR. Thus, HL of MD-DG is caused by impaired Schwann cell-mediated myelination at the peripheral cochlear nerve.