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Defective secretion of saliva in transgenic mice lacking aquaporin-5 water channels
Author(s): Ma TH, Song YL, Gillespie A, Carlson EJ, Epstein CJ, Verkman AS
Source: JOURNAL OF BIOLOGICAL CHEMISTRY    Volume: 274    Issue: 29    Pages: 20071-20074    Published: JUL 16 1999  
Times Cited: 202     References: 26     
Abstract: Aquaporin-6 (AQP5) is a water selective transporting protein expressed in epithelial cells of serous acini in salivary gland. We generated AQP5 null mice by targeted gene disruption. The genotype distribution from intercross of founder AQP5 heterozygous mice was 70: 69:29 wild-type:heterozygote:knockout, indicating impaired prenatal survival of the null mice. The knockout mice had grossly normal appearance, but grew similar to 20% slower than litter-matched wild-type mice when placed on solid food after weaning. Pilocarpine-stimulated saliva production was reduced by more than 60% in AQP5 knockout mice. Compared with the saliva from wild-type mice, the saliva from knockout mice was hypertonic (420 mosM) and dramatically more viscous. Amylase and protein secretion, functions of salivary mucous cells, were not affected by AQP5 deletion. Water channels AQP1 and AQP4 have also been localized to salivary gland; however, pilocarpine stimulation studies showed no defect in the volume or composition of saliva in AQP1 and AQP4 knockout mice. These results implicate a key role for AQP5 in saliva fluid secretion and provide direct evidence that high epithelial cell membrane water permeability is required for active, near-isosmolar fluid transport.
Document Type: Article
Language: English
Reprint Address: Verkman, AS (reprint author), Univ Calif San Francisco, Cardiovasc Res Inst, Dept Med, 1246 Hlth Sci E Tower, San Francisco, CA 94143 USA
Addresses:
1. Univ Calif San Francisco, Cardiovasc Res Inst, Dept Med, San Francisco, CA 94143 USA
2. Univ Calif San Francisco, Cardiovasc Res Inst, Dept Physiol, San Francisco, CA 94143 USA
3. Univ Calif San Francisco, Cardiovasc Res Inst, Dept Pediat, San Francisco, CA 94143 USA
Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
Subject Category: Biochemistry & Molecular Biology
IDS Number: 216JE
ISSN: 0021-9258
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