title: Precise toxigenic ablation of intermediate cells abolishes the "battery" of the cochlear duct.
abstract: The extracellular potential of excitable and nonexcitable cells with respect to ground is ∼0 mV. One of the known exceptions in mammals is the cochlear duct, where the potential is ∼80-100 mV, called the endocochlear potential (EP). The EP serves as the "battery" for transduction of sound, contributing toward the sensitivity of the auditory system. The stria vascularis (StV) of the cochlear duct is the station where the EP is generated, but the cell-specific roles in the StV are ill defined. Using the intermediate cell (IC)-specific tyrosinase promoter, under the control of diphtheria toxin (DT), we eliminated and/or halted differentiation of neural crest melanocytes after migration to the StV. The ensuing adult transgenic mice are profoundly deaf. Additionally, the EP was abolished. Expression of melanocyte early marker and Kir4.1 in ICs precedes the onset of pigment synthesis. Activation of DT leads to loss of ICs. Finally, in accord with the distinct embryology of retinal pigmented cells, transgenic mice with toxigenic ablation of neural crest-derived melanocytes have intact visual responses. We assert that the tyrosinase promoter is the distinct target for genetic manipulation of IC-specific genes.
authors.affiliation: Center for Neuroscience, Program in Communication Science, University of California-Davis, Davis, California 95618, USA.
authors.forename: Hyo Jeong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Michael Anne
authors.initials: MA
authors.lastname: Gratton
authors.forename: Jeong-Han
authors.initials: JH
authors.lastname: Lee
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Perez Flores
authors.forename: Wenying
authors.initials: W
authors.lastname: Wang
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Doyle
authors.forename: Friedrich
authors.initials: F
authors.lastname: Beermann
authors.forename: Michael A
authors.initials: MA
authors.lastname: Crognale
authors.forename: Ebenezer N
authors.initials: EN
authors.lastname: Yamoah
mesh_terms: D000200:Action Potentials; D000818:Animals; D002454:Cell Differentiation; D003638:Deafness / Q000235:genetics*; D004167:Diphtheria Toxin / Q000235:genetics* / Q000378:metabolism; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D014442:Monophenol Monooxygenase / Q000235:genetics; D009432:Neural Crest / Q000166:cytology / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000378:metabolism; D013316:Stria Vascularis / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D019076:Transgenes / Q000235:genetics*; D014785:Vision, Ocular / Q000235:genetics; D000098854:Kcnj10 Channel
chemical_list: D004167:Diphtheria Toxin; D000098854:Kcnj10 Channel; D024661:Potassium Channels, Inwardly Rectifying; D014442:Monophenol Monooxygenase