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 β‐galactosidase activity. Saposin A and C, the heat‐stable small sphingolipid activator glycoproteins, stimulate the activity of galactosylceramide β‐galactosidase as well as glucosylceramide β‐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 β‐glucosidase (measured by hydrolysis of 4‐methylumbelliferyl‐β‐glucoside) with similar preparations from control tissues. The effect on the activity of galactosylceramide 4bT‐galactosidase as well as 4‐methylum‐belliferyl‐β‐glucoside β‐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 β‐galactosidase.