Abstract
Mutations of gap junction connexin genes induce a high incidence of nonsyndromic hearing loss. Pannexin genes also encode gap junctional proteins in vertebrates. Recent studies demonstrated that Pannexin-1 (Panx1) deficiency in mice and mutation in humans are also associated with hearing loss. So far, several Panx1 knockout (KO) mouse lines were established. In general, these Panx1 KO mouse lines demonstrate consistent phenotypes in most aspects, including hearing loss. However, a recent study reported that a Panx1 KO mouse line, which was created by Genentech Inc., had no hearing loss as measured by the auditory brainstem response (ABR) threshold at low-frequency range (<24 kHz). Here, we used multiple auditory function tests and re-examined hearing function in the Genentech Panx1 (Gen-Panx1) KO mouse. We found that ABR thresholds in the Gen-Panx1 KO mouse were significantly increased, in particular, in the high-frequency region. Moreover, consistent with the increase in ABR threshold, distortion product otoacoustic emission (DPOAE) and cochlear microphonics (CM), which reflect active cochlear amplification and auditory receptor current, respectively, were significantly reduced. These data demonstrated that the Gen-Panx1 KO mouse has hearing loss and further confirmed that Panx1 deficiency can cause deafness.
Highlights
Gap junctions play a critical role in hearing
It has been found that mutations in the Connexin26 (Cx26, GJB2) gap junctional gene induce a high incidence of hearing loss, accounting for more than 50% of the cases of nonsyndromic hearing loss [1,2,3,4,5]
We found that the Gen-Panx1 KO mice have hearing loss, in the high-frequency region, which is consistent with hearing loss observed in Foxg1-Panx1 conditional knockout mice [21], and in Pax2-Panx1 cKO mice [30]
Summary
Gap junctions play a critical role in hearing. It has been found that mutations in the Connexin (Cx26, GJB2) gap junctional gene induce a high incidence of hearing loss, accounting for more than 50% of the cases of nonsyndromic hearing loss [1,2,3,4,5]. The pannexin gene family encodes gap junctional proteins in vertebrates. In the mammalian inner ear, pannexins have extensive expression; all three pannexin isoforms have expression in the inner ear [8]. Auditory sensory hair cells have no expression of pannexins [8]. These distinctive cellular distributions strongly suggest that pannexins may have important functions in hearing
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.