title: Downregulation of otospiralin, a novel inner ear protein, causes hair cell degeneration and deafness.
abstract: Mesenchymal nonsensory regions of the inner ear are important structures surrounding the neurosensory epithelium that are believed to participate in the ionic homeostasis of the cochlea and vestibule. We report here the discovery of otospiralin, an inner ear-specific protein that is produced by fibrocytes from these regions, including the spiral ligament and spiral limbus in the cochlea and the maculae and semicircular canals in the vestibule. Otospiralin is a novel 6.4 kDa protein of unknown function that shares a protein motif with the gag p30 core shell nucleocapsid protein of type C retroviruses. To evaluate its functional importance, we downregulated otospiralin by cochlear perfusion of antisense oligonucleotides in guinea pigs. This led to a rapid threshold elevation of the compound action potentials and irreversible deafness. Cochlear examination by transmission electron microscopy revealed hair cell loss and degeneration of the organ of Corti. This demonstrates that otospiralin is essential for the survival of the neurosensory epithelium.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U. 254, Laboratoire de Neurobiologie de l'Audition, 34090 Montpellier, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Delprat
authors.forename: Ana
authors.initials: A
authors.lastname: Boulanger
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Vicky
authors.initials: V
authors.lastname: Beaudoin
authors.forename: Matthieu J
authors.initials: MJ
authors.lastname: Guitton
authors.forename: Stephanie
authors.initials: S
authors.lastname: Ventéo
authors.forename: Claude J
authors.initials: CJ
authors.lastname: Dechesne
authors.forename: Rémy
authors.initials: R
authors.lastname: Pujol
authors.forename: Mireille
authors.initials: M
authors.lastname: Lavigne-Rebillard
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Puel
authors.forename: Christian P
authors.initials: CP
authors.lastname: Hamel
mesh_terms: D000161:Acoustic Stimulation; D000200:Action Potentials / Q000187:drug effects; D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003051:Cochlea / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003056:Cochlear Nerve / Q000502:physiology; D003638:Deafness / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D007758:Ear, Inner / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D009928:Organ Specificity; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects; D014176:Protein Biosynthesis; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017386:Sequence Homology, Amino Acid
chemical_list: C503045:OTOS protein, human; D016376:Oligonucleotides, Antisense; C503046:Otos protein, mouse; C503047:Otos protein, rat; D011506:Proteins; D012333:RNA, Messenger