title: Deletion of Tricellulin Causes Progressive Hearing Loss Associated with Degeneration of Cochlear Hair Cells.
abstract: Tricellulin (also known as MARVELD2) is considered as a central component of tricellular tight junctions and is distributed among various epithelial tissues. Although mutations in the gene encoding tricellulin are known to cause deafness in humans (DFNB49) and mice, the influence of its systemic deletion in vivo remains unknown. When we generated tricellulin-knockout mice (Tric(-/-)), we found an early-onset rapidly progressive hearing loss associated with the degeneration of hair cells (HCs); however, their body size and overall appearance were normal. Tric(-/-) mice did not show any morphological change pertaining to other organs such as the gastrointestinal tract, liver, kidney, thyroid gland and heart. The endocochlear potential (EP) was normal in Tric(-/-) mice, suggesting that the tight junction barrier is maintained in the stria vascularis, where EP is generated. The degeneration of HCs, which occurred after the maturation of EP, was prevented in the culture medium with an ion concentration similar to that of the perilymph. These data demonstrate the specific requirement of tricellulin for maintaining ion homeostasis around cochlear HCs to ensure their survival. The Tric(-/-) mouse provides a new model for understanding the distinct roles of tricellulin in different epithelial systems as well as in the pathogenesis of DFNB49.
authors.affiliation: Laboratory of Biological Science, Graduate School of Frontier Biosciences and Graduate School of Medicine, Osaka University, Osaka 565-0781, Japan.|Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Kamitani
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Sakaguchi
authors.affiliation: Laboratory of Biological Science, Graduate School of Frontier Biosciences and Graduate School of Medicine, Osaka University, Osaka 565-0781, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tamura
authors.affiliation: Department of Otolaryngology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan.
authors.forename: Takenori
authors.initials: T
authors.lastname: Miyashita
authors.affiliation: Laboratory of Biological Science, Graduate School of Frontier Biosciences and Graduate School of Medicine, Osaka University, Osaka 565-0781, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yamazaki
authors.affiliation: Laboratory of Biological Science, Graduate School of Frontier Biosciences and Graduate School of Medicine, Osaka University, Osaka 565-0781, Japan.
authors.forename: Reitaro
authors.initials: R
authors.lastname: Tokumasu
authors.affiliation: Department of Otolaryngology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan.
authors.forename: Ryuhei
authors.initials: R
authors.lastname: Inamoto
authors.affiliation: Department of Otolaryngology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Matsubara
authors.affiliation: Department of Otolaryngology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan.|Present address: Osaka Bay Central Hospital, Osaka 552-0021, Japan.
authors.forename: Nozomu
authors.initials: N
authors.lastname: Mori
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Hisa
authors.affiliation: Laboratory of Biological Science, Graduate School of Frontier Biosciences and Graduate School of Medicine, Osaka University, Osaka 565-0781, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tsukita
mesh_terms: D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D006198:Hair Cells, Auditory / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D034381:Hearing Loss / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D062794:MARVEL Domain Containing 2 Protein / Q000172:deficiency / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D010539:Permeability; D013316:Stria Vascularis / Q000378:metabolism; D019108:Tight Junctions / Q000473:pathology / Q000648:ultrastructure
chemical_list: D062794:MARVEL Domain Containing 2 Protein