title: Mice lacking ganglioside GM3 synthase exhibit complete hearing loss due to selective degeneration of the organ of Corti.
abstract: The ganglioside GM3 synthase (SAT-I), encoded by a single-copy gene, is a primary glycosyltransferase for the synthesis of complex gangliosides. In SAT-I null mice, hearing ability, assessed by brainstem auditory-evoked potentials (BAEP), was impaired at the onset of hearing and had been completely lost by 17 days after birth (P17), showing a deformity in hair cells in the organ of Corti. By 2 months of age, the organ of Corti had selectively and completely disappeared without effect on balance or motor function or in the histology of vestibule. Interestingly, spatiotemporal changes in localization of individual gangliosides, including GM3 and GT1b, were observed during the postnatal development and maturation of the normal inner ear. GM3 expressed in almost all regions of cochlea at P3, but at the onset of hearing it distinctly localized in stria vascularis, spiral ganglion, and the organ of Corti. In addition, SAT-I null mice maintain the function of stria vascularis, because normal potassium concentration and endocochlear potential of endolymph were observed even when they lost the BAEP completely. Thus, the defect of hearing ability of SAT-I null mice could be attributed to the functional disorganization of the organ of Corti, and the expression of gangliosides, especially GM3, during the early part of the functional maturation of the cochlea could be essential for the acquisition and maintenance of hearing function.
authors.affiliation: Division of Glycopathology, Institute of Molecular Biomembranes and Glycobiology, Tohoku Pharmaceutical University, Sendai, Miyagi, Japan.
authors.forename: Misato
authors.initials: M
authors.lastname: Yoshikawa
authors.forename: Shinji
authors.initials: S
authors.lastname: Go
authors.forename: Kotaro
authors.initials: K
authors.lastname: Takasaki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kakazu
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Ohashi
authors.forename: Masakazu
authors.initials: M
authors.lastname: Nagafuku
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kabayama
authors.forename: Junji
authors.initials: J
authors.lastname: Sekimoto
authors.forename: Shun-ichi
authors.initials: S
authors.lastname: Suzuki
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Takaiwa
authors.forename: Takashi
authors.initials: T
authors.lastname: Kimitsuki
authors.forename: Nozomu
authors.initials: N
authors.lastname: Matsumoto
authors.forename: Shizuo
authors.initials: S
authors.lastname: Komune
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kamei
authors.forename: Masaki
authors.initials: M
authors.lastname: Saito
authors.forename: Michihiro
authors.initials: M
authors.lastname: Fujiwara
authors.forename: Katsunori
authors.initials: K
authors.lastname: Iwasaki
authors.forename: Jin-ichi
authors.initials: J
authors.lastname: Inokuchi
mesh_terms: D000818:Animals; D003638:Deafness / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009154:Mutation; D009925:Organ of Corti / Q000196:embryology / Q000502:physiology*; D013216:Reflex, Startle; D012799:Sialyltransferases / Q000235:genetics* / Q000378:metabolism*; D013316:Stria Vascularis / Q000502:physiology
chemical_list: D012799:Sialyltransferases; C021343:haematoside synthetase