1. Department of Otology and Laryngology, Harvard Medical School and Eaton-Peabody Laboratory, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts 02114, USA
2. Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA
3. Boys Town National Research Hospital, Omaha, Nebraska 68131, USA
4. Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA
5. These authors contributed equally to this work

Correspondence to: Jian Zuo³ Correspondence and requests for materials should be addressed to J.Z. (e-mail: Email: jian.zuo@stjude.org).

Abstract

Hearing sensitivity in mammals is enhanced by more than 40 dB (that is, 100-fold) by mechanical amplification thought to be generated by one class of cochlear sensory cells, the outer hair cells^{1, 2, 3, 4}. In addition to the mechano-electrical transduction required for auditory sensation, mammalian outer hair cells also perform electromechanical transduction, whereby transmembrane voltage drives cellular length changes at audio frequencies in vitro^{5, 6, 7}. This electromotility is thought to arise through voltage-gated conformational changes in a membrane protein^{8, 9}, and prestin has been proposed as this molecular motor^{10, 11, 12}. Here we show that targeted deletion of prestin in mice results in loss of outer hair cell electromotility in vitro and a 40–60 dB loss of cochlear sensitivity in vivo, without disruption of mechano-electrical transduction in outer hair cells. In heterozygotes, electromotility is halved and there is a twofold (about 6 dB) increase in cochlear thresholds. These results suggest that prestin is indeed the motor protein, that there is a simple and direct coupling between electromotility and cochlear amplification, and that there is no need to invoke additional active processes to explain cochlear sensitivity in the mammalian ear.