High levels of GM1-ganglioside beta-galactosidase in the salivary glands and GM1-like-ganglioside storage in parotids of deficient mice

We have previously demonstrated high levels of GM1-ganglioside beta-galacto sidase (beta-gal) in the salivary glands of Swiss-Webster mice (Nowroozi et al., J Craniofac Genet Dev Biol 18:51, 1998), and suggested that this acti vity reflects an important role for the lysosome in catabolism of salivary glycoconjugates. Here, we characterized and compared activities of lysosoma l glycosidases among the salivary glands, spleen, and muscle of C57BL/6 mic e. beta-gal, hexosaminidase, and beta-glucuronidase activities are high in all three glands relative to muscle. Enzyme activities in the sublingual gl and were substantially higher than in the submandibular and parotid glands. Spleen displays levels of activity that are comparable or higher (for beta -glucuronidase) than those in the salivary glands, whereas muscle displays substantially lower levels of these lysosomal glycosidases. In order to inv estigate the role of beta-gal in the salivary,glands, we further characteri zed the salivary phenotype of knock-out mice deficient in this enzyme, mimi cking human GM1-gangliosidosis. In contrast with the relative levels of bet a-gal specific-activity among the salivary glands, only the parotid develop ed severe, generalized, degenerative histopathological changes in beta-gal- deficient knock-out mice. GM1-like-ganglioside, typically found at high lev els only in the nerve tissue, where its exact function is still not clear, was demonstrated in storage vacuoles of the parotid glands of the deficient mice by binding of cholera toxin subunit B. Thus, beta-gal activity observ ed in the parotid gland most likely reflects its role in GM1-ganglioside ca tabolism, and this ganglioside, never previously reported in the salivary g lands, may have a role in parotid exocrine secretory functions. beta-gal ma y also serve in secretory glycoprotein catabolism in other salivary glands, but this function may be non-essential for these glands.