The biochemical pathogenesis of globoid cell leukodystrophy (GLD) (Krabbe disease) was investigated in vitro using the cultured neural cells obtained from dorsal root ganglion (DRG) of twitcher mouse (murine Krabbe disease). Electron microscopic examination of twitcher DRG of 30 days old showed the demyelination and abnormal inclusion bodies, whereas mitochondrial structure appeared to be intact. Cultured neural cells from control mice were well proliferated to form the network processes, while those from twitcher were decreased in cell numbers and showed the vacuolation of cell body, degeneration of processes, and finally died after three weeks. There was no apparent difference of lipid compositions between control and twitcher DRG, and the galactocerebroside levels from control were similar to those of twitcher. However, marked accumulation of psychosine was found in the 30-day-old-twicher DRG. The level of psychosine from twitcher DRG was elevated approximately 70 to 80-fold compared with those of control. These data suggest that neural cells from twitcher mice degenerative with age also in vitro and accumulation of psychosine in twitcher DRG may play an important role for the demyelination in GLD. © 1990, All rights reserved.
