title: Saposins (sphingolipid activator proteins) in the twitcher mutant mouse.
abstract: The twitcher mutant mouse, the animal model of Krabbe disease (human globoid cell leukodystrophy), is characterized by apparent deficiency of galactosylceramide beta-galactosidase activity. Saposin A and C, the heat-stable small sphingolipid activator glycoproteins, stimulate the activity of galactosylceramide beta-galactosidase as well as glucosylceramide beta-glucoside. The role of these saposins in the twitcher mutation was investigated. Boiled supernatant fractions, which contained saposins, were prepared from homogenates of twitcher brain, liver, kidney, and spleen. These preparations showed an almost identical effect on the activity of purified glucosylceramide beta-glucosidase (measured by hydrolysis of 4-methylumbelliferyl-beta-glucoside) with similar preparations from control tissues. The effect on the activity of galactosylceramide beta-galactosidase as well as 4-methylumbelliferyl-beta-glucoside beta-glucosidase in the twitcher brain and liver homogenates by authentic saposin A and C was similar to that in control tissues. These results suggest that the twitcher mutation does not affect the concentrations of saposin A or C or their interaction with galactosylceramide beta-galactosidase.
authors.affiliation: Department of Neurosciences, School of Medicine, University of California, San Diego, La Jolla.
authors.forename: H
authors.initials: H
authors.lastname: Shigematsu
authors.forename: S
authors.initials: S
authors.lastname: Morimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Kishimoto
authors.forename: S
authors.initials: S
authors.lastname: Weiler
authors.forename: J
authors.initials: J
authors.lastname: Tomich
authors.forename: J
authors.initials: J
authors.lastname: Barranger
authors.forename: M
authors.initials: M
authors.lastname: Shinohara
authors.forename: A M
authors.initials: AM
authors.lastname: Yeager
authors.forename: J S
authors.initials: JS
authors.lastname: O'Brien
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology; D006023:Glycoproteins / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants / Q000378:metabolism*; D011506:Proteins / Q000494:pharmacology*; D012016:Reference Values; D049231:Saposins; D001617:beta-Glucosidase / Q000378:metabolism
chemical_list: D006023:Glycoproteins; D011506:Proteins; D049231:Saposins; D001617:beta-Glucosidase