Impaired hearing in mice lacking aquaporin-4 water channels

A role for aquaporins (AQPs) in hearing has been suggested from the specifi c expression of aquaporins in inner ear and the need for precise volume reg ulation in epithelial cells involved in acoustic signal transduction. Using mice deficient in selected aquaporins as controls, we localized AQP1 in fi brocytes in the spiral ligament and AQP4 in supporting epithelial cells (He nsen's, Claudius, and inner sulcus cells) in the organ of Corti. To determi ne whether aquaporins play a role in hearing, auditory brain stem response (ABR) thresholds were compared in wild-type mice and transgenic null mice l acking (individually) AQP1, AQP3, AQP4, and AQP5. In 4-5-week-old mice in a CD1 genetic background, ABR thresholds in response to a click stimulus wer e remarkably increased by > 12 db in AQP4 null mice compared with wild-type mice (p < 0.001), whereas ABR thresholds were not affected by AQP1, AQP3, or AQP5 deletion. In a C57/b16 background, nearly all AQP4 null mice were d eaf, whereas ABRs could be elicited in wildtype controls. ABRs in AQP4 null CD1 mice measured in response to tone bursts (4-20 kHz) indicated a freque ncy-independent hearing deficit. Light microscopy showed no differences in cochlear morphology of wildtype versus AQP4 null mice. These results provid e the first direct evidence that an aquaporin water channel plays a role in hearing. AQP4 may facilitate rapid osmotic equilibration in epithelial cel ls in the organ of Corti, which are subject to large K+ fluxes during mecha no-electric signal transduction.