title: Pannexin 1 deficiency can induce hearing loss.
abstract: Gap junctions play a critical role in hearing. Connexin gap junction gene mutations can induce a high incidence of hearing loss. Pannexin (Panx) gene also encodes gap junction proteins in vertebrates. Panx1 is a predominant pannexin isoform and has extensive expression in the cochlea. Here, we report that deletion of Panx1 in the cochlea could produce a progressive hearing loss. The auditory brainstem response (ABR) recording showed that hearing loss was moderate to severe and severe at high-frequencies. Distortion product otoacoustic emission (DPOAE), which reflects the activity of active cochlear mechanics that can amply acoustic stimulation to enhance hearing sensitivity and frequency selectivity, was also reduced. We further found that Panx1 deficiency could activate Caspase-3 cell apoptotic pathway in the cochlea to cause hair cells and other types of cells degeneration. These data indicate that like connexins Panx1 deficiency can also induce hearing loss. These data also suggest that pannexins play important rather than redundant roles in the cochlea and hearing.
authors.affiliation: Department of Otolaryngology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536, United States. Electronic address: hzhao2@uky.edu.
authors.forename: Hong-Bo
authors.initials: HB
authors.lastname: Zhao
authors.affiliation: Department of Otolaryngology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536, United States.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Otolaryngology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536, United States.
authors.forename: Chun
authors.initials: C
authors.lastname: Liang
authors.affiliation: Department of Otolaryngology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536, United States.
authors.forename: Jin
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D003051:Cochlea / Q000473:pathology / Q000503:physiopathology; D017630:Connexins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem; D034381:Hearing Loss / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D017084:Otoacoustic Emissions, Spontaneous
chemical_list: D017630:Connexins; D009419:Nerve Tissue Proteins; C503631:Panx1 protein, mouse; C505409:Casp3 protein, mouse; D053148:Caspase 3
keywords: Caspasae-3; Cell degeneration; Deafness; Gap junction; Inner ear; Pannexin 1