Impaired hearing in mice lacking aquaporin-4 water channels.
A role for aquaporins (AQPs) in hearing has been suggested from the specific expression of aquaporins in inner ear and the need for precise volume regulation in epithelial cells involved in acoustic signal transduction. Using mice deficient in selected aquaporins as controls, we localized AQP1 in fibrocytes in the spiral ligament and AQP4 in supporting epithelial cells (Hensen's, Claudius, and inner sulcus cells) in the organ of Corti. To determine whether aquaporins play a role in hearing, auditory brain stem response (ABR) thresholds were compared in wild-type mice and transgenic null mice lacking (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 were 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/bl6 background, nearly all AQP4 null mice were deaf, whereas ABRs could be elicited in wild-type controls. ABRs in AQP4 null CD1 mice measured in response to tone bursts (4-20 kHz) indicated a frequency-independent hearing deficit. Light microscopy showed no differences in cochlear morphology of wild-type versus AQP4 null mice. These results provide the first direct evidence that an aquaporin water channel plays a role in hearing. AQP4 may facilitate rapid osmotic equilibration in epithelial cells in the organ of Corti, which are subject to large K(+) fluxes during mechano-electric signal transduction.
Li
J
J
Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, California 94143-0521, USA.
Verkman
A S
AS
D000818:Animals; D051398:Aquaporin 1; D051401:Aquaporin 4; D020346:Aquaporins / Q000502:physiology*; D016057:Evoked Potentials, Auditory, Brain Stem; D006311:Hearing Disorders / Q000209:etiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011188:Potassium / Q000378:metabolism
C496021:Aqp1 protein, mouse; C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D020346:Aquaporins; D051398:Aquaporin 1; D011188:Potassium