AUTHOR=Zorzi Veronica , Paciello Fabiola , Ziraldo Gaia , Peres Chiara , Mazzarda Flavia , Nardin Chiara , Pasquini Miriam , Chiani Francesco , Raspa Marcello , Scavizzi Ferdinando , Carrer Andrea , Crispino Giulia , Ciubotaru Catalin D. , Monyer Hannah , Fetoni Anna R. , M. Salvatore Anna , Mammano Fabio 

TITLE=Mouse Panx1 Is Dispensable for Hearing Acquisition and Auditory Function

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=10

YEAR=2017

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2017.00379

DOI=10.3389/fnmol.2017.00379

ISSN=1662-5099

ABSTRACT=<p>Panx1 forms plasma membrane channels in brain and several other organs, including the inner ear. Biophysical properties, activation mechanisms and modulators of Panx1 channels have been characterized in detail, however the impact of <italic>Panx1</italic> on auditory function is unclear due to conflicts in published results. To address this issue, hearing performance and cochlear function of the <italic>Panx1</italic>−/− mouse strain, the first with a reported global ablation of <italic>Panx1</italic>, were scrutinized. Male and female homozygous (<italic>Panx1</italic>−/−), hemizygous (<italic>Panx1</italic>+/−) and their wild type (WT) siblings (<italic>Panx1</italic>+/+) were used for this study. Successful ablation of <italic>Panx1</italic> was confirmed by RT-PCR and Western immunoblotting in the cochlea and brain of <italic>Panx1</italic>−/− mice. Furthermore, a previously validated Panx1-selective antibody revealed strong immunoreactivity in WT but not in <italic>Panx1</italic>−/− cochleae. Hearing sensitivity, outer hair cell-based “cochlear amplifier” and cochlear nerve function, analyzed by auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) recordings, were normal in <italic>Panx1</italic>+/− and <italic>Panx1</italic>−/− mice. In addition, we determined that global deletion of <italic>Panx1</italic> impacts neither on connexin expression, nor on gap-junction coupling in the developing organ of Corti. Finally, spontaneous intercellular Ca<sup>2+</sup> signal (ICS) activity in organotypic cochlear cultures, which is key to postnatal development of the organ of Corti and essential for hearing acquisition, was not affected by <italic>Panx1</italic> ablation. Therefore, our results provide strong evidence that, in mice, <italic>Panx1</italic> is dispensable for hearing acquisition and auditory function.</p>