Defective secretion of saliva in transgenic mice lacking aquaporin-5 waterchannels

Aquaporin-6 (AQP5) is a water selective transporting protein expressed in e pithelial cells of serous acini in salivary gland. We generated AQP5 null m ice by targeted gene disruption. The genotype distribution from intercross of founder AQP5 heterozygous mice was 70: 69:29 wild-type:heterozygote:knoc kout, indicating impaired prenatal survival of the null mice. The knockout mice had grossly normal appearance, but grew similar to 20% slower than lit ter-matched wild-type mice when placed on solid food after weaning. Pilocar pine-stimulated saliva production was reduced by more than 60% in AQP5 knoc kout mice. Compared with the saliva from wild-type mice, the saliva from kn ockout mice was hypertonic (420 mosM) and dramatically more viscous. Amylas e and protein secretion, functions of salivary mucous cells, were not affec ted by AQP5 deletion. Water channels AQP1 and AQP4 have also been localized to salivary gland; however, pilocarpine stimulation studies showed no defe ct in the volume or composition of saliva in AQP1 and AQP4 knockout mice. T hese results implicate a key role for AQP5 in saliva fluid secretion and pr ovide direct evidence that high epithelial cell membrane water permeability is required for active, near-isosmolar fluid transport.