Nervous System Origin of Renal Galactosylceramide in the Twitcher Mouse Mutant

Abstract

Globoid cell leukodystrophy (GLD, Krabbe disease) is a rare genetic disorder caused by a catalyc deficiency of galactosylceramide (EC 3.2.1.46) (Suzuki and Suzuki, 1970). One of the unusual features of the disease is the absence of abnormal accumulation of galactosylceramide in the nervous system or in the kidney despite the genetic block in its degradative pathway (Suzuki, 1971; Vanier and Svennerholm, 1974). Genetically equivalent diseases with similar clinical and pathological manifestations occur in the dog, mouse, sheep, and probably also in the cat (Suzuki and Suzuki, 1985). In the central nervous system of affected dogs and mice, abnormal accumulation of galactosylceramide also does not occur. In contrast, an enormous accumulation of galactosylceramide is observed in the kidney of affected mice (the twitcher mutant) (Ida et al., 1982; Igisu et al., 1983) and to a lesser extent in the kidney of affected dogs (Igisu, Katayama and Suzuki, unpublished observations).