The twitcher mouse: accumulation of galactosylsphingosine and pathology of the sciatic nerve

Morphological and biochemical changes were investigated in the early developmental stages of sciatic nerve of the twitcher mouse, a murine model of human globoid cell leukodystrophy. The concentration of galactosylsphingosine (psychosine) and the chronological changes of the twitcher mouse peripheral nerve pathology correlated well. Galactosylsphingosine had already accumulated at birth and dramatically increased with age. Characteristic inclusions were observed in Schwann cells and macrophages of the twitcher mouse on the 5th postnatal day. Endoneurial edema developed after 10 postnatal days and the hypomyelination was pronounced at 15-20 postnatal days. These findings suggest that galactosylsphingosine is cytotoxic for myelin-forming cells and is closely related to pathogenetic events in the twitcher mouse.