The twitcher mouse: degeneration of oligodendrocytes in vitro.

Oligodendrocytes were isolated from the brain of the twitcher (twi/twi), an authentic murine model of globoid cell leukodystrophy (GLD), carrier (+/twi) and their littermate controls (+/+) and were maintained in vitro for 24 days. By 4 days in vitro (4 DIV) oligodendrocytes developed thorny processes and their morphology were closely similar to each other regardless of their genetic status. After 17 DIV, however, oligodendrocytes in twi/twi progressively degenerated and only 12% of oligodendrocytes counted at 10 DIV survived at 24 DIV in twi/twi, while in +/twi and +/+, mean survival rates were 85 and 83% respectively. Characteristic inclusions of GLD were detected in the perikarya of degenerating twi/twi oligodendrocytes indicating that metabolic defect was expressed even in isolated oligodendrocytes. These results further support the hypothesis that the primary pathogenetic event in murine GLD, twitcher, is degeneration of oligodendrocytes due to progressive accumulation of the toxic metabolite, galactosylsphingosine (psychosine).