A novel animal model for dry mouth: E2f1-deficient NOD/SCID mice

Abstract It is well known that hyposecretion of saliva and consequent dry mouth can lead to severe dental caries, periodontal disease, and mucosal infections. To investigate the mechanisms of hyposalivation, a dry mouth animal model is required. Recently, we established E2f1-deficient non-obese diabetic/severe combined immunodeficiency disease (NOD/SCID.E2f1 −/− ) mice. In this article, we review NOD/SCID.E2f1 −/− mice, which are a convenient in vivo model for dry mouth. Behavioral analyses of NOD/SCID.E2f1 −/− mice revealed that they increased water consumption when they ate dry food, and that the frequency and time these mice spent on water intake were higher and longer than that observed in control mice. In NOD/SCID.E2f1 −/− mice, the volume of secreted saliva stimulated with secretagogue was less than that for the control mice. Histological analyses of the salivary glands revealed that NOD/SCID.E2f1 −/− mice had more salivary ducts than control mice. Immunohistochemical analyses of the salivary acini revealed that the localization of aqaporin-5 (AQP5), a water channel that is involved in salivary fluid secretion, differed in NOD/SCID.E2f1 −/− mice when compared to control mice; AQP5 was leaky and diffusively localized from the apical membrane to the cytosol in the NOD/SCID.E2f1 −/− mice. Covalent modification by ubiquitination of AQP5 was detected in the salivary glands of NOD/SCID.E2f1 −/− mice, suggesting that the changes in acinar/duct structure and the down-regulation of AQP5 in the salivary gland caused the pathogenesis of hyposalivation observed in the NOD/SCID.E2f1 −/− mice. Furthermore, the mutant mice did not have any underlying diseases, such as diabetes. Therefore NOD/SCID.E2f1 −/− mice may provide a useful animal model for dry mouth.