title: Partial requirement of endothelin receptor B in spiral ganglion neurons for postnatal development of hearing.
abstract: Impairments of endothelin receptor B (Ednrb/EDNRB) cause the development of Waardenburg-Shah syndrome with congenital hearing loss, hypopigmentation, and megacolon disease in mice and humans. Hearing loss in Waardenburg-Shah syndrome has been thought to be caused by an Ednrb-mediated congenital defect of melanocytes in the stria vascularis (SV) of inner ears. Here we show that Ednrb expressed in spiral ganglion neurons (SGNs) in inner ears is required for postnatal development of hearing in mice. Ednrb protein was expressed in SGNs from WT mice on postnatal day 19 (P19), whereas it was undetectable in SGNs from WT mice on P3. Correspondingly, Ednrb homozygously deleted mice (Ednrb(-/-) mice) with congenital hearing loss showed degeneration of SGNs on P19 but not on P3. The congenital hearing loss involving neurodegeneration of SGNs as well as megacolon disease in Ednrb(-/-) mice were markedly improved by introducing an Ednrb transgene under control of the dopamine β-hydroxylase promoter (Ednrb(-/-);DBH-Ednrb mice) on P19. Neither defects of melanocytes nor hypopigmentation in the SV and skin in Ednrb(-/-) mice was rescued in the Ednrb(-/-);DBH-Ednrb mice. Thus, the results of this study indicate a novel role of Ednrb expressed in SGNs distinct from that in melanocytes in the SV contributing partially to postnatal hearing development.
authors.affiliation: Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai, Aichi, Japan.
authors.forename: Michiru
authors.initials: M
authors.lastname: Ida-Eto
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Ohgami
authors.forename: Machiko
authors.initials: M
authors.lastname: Iida
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yajima
authors.forename: Mayuko Y
authors.initials: MY
authors.lastname: Kumasaka
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Takaiwa
authors.forename: Takashi
authors.initials: T
authors.lastname: Kimitsuki
authors.forename: Michihiko
authors.initials: M
authors.lastname: Sone
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakashima
authors.forename: Toyonori
authors.initials: T
authors.lastname: Tsuzuki
authors.forename: Shizuo
authors.initials: S
authors.lastname: Komune
authors.forename: Masashi
authors.initials: M
authors.lastname: Yanagisawa
authors.forename: Masashi
authors.initials: M
authors.lastname: Kato
mesh_terms: D000818:Animals; D006309:Hearing / Q000502:physiology*; D034381:Hearing Loss / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008544:Melanocytes / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism*; D010858:Pigmentation / Q000235:genetics; D017466:Receptors, Endothelin / Q000235:genetics / Q000378:metabolism*; D013136:Spiral Ganglion / Q000254:growth & development / Q000378:metabolism*
chemical_list: D017466:Receptors, Endothelin