Comparison of the behavior of neural stem cells in the brain of normal and twitcher mice after neonatal transplantation.

The twitcher mouse is a model of human Krabbe's disease caused by a mutation in the galacto-cerebrosidase gene. As a result of deficient catabolism of myelin, death of oligodendrocytes and demyelination occur widely in the central and peripheral nervous system, making it an ideal model for investigation of myelin repair strategies. Here we describe the use of mouse neural stem cells (NSCs) expressing enhanced green fluorescence protein (eGFP) for transplantation in neonatal normal and twitcher mice. Normal and twitcher mice in all age groups (20, 30, and 45 days old) showed engraftment and differentiation of injected cells. The engrafted cells were found in the ventricles and a wide range of regions in the brain parenchyma. There was no significant difference in the total number of cells engrafted and the pattern of engraftment between 30-day-old normal and twitcher mice. The average number of engrafted cells in the brain of a 30-day-old mouse was 964 +/- 281 (n = 8). Engrafted cells with the morphology of neurons, astrocytes, and oligodendrocytes were identified. Differentiation into oligodendrocytes was confirmed by immunohistochemical staining using a cell-type-specific marker. There was a higher percentage of cells engrafted in the grey matter than in the white matter (p < 0.01) in both normal and twitcher mouse brain. This study indicates that the environment of demyelination in 30-day-old twitcher mouse brain has not significantly altered the engraftment and distribution patterns of NSCs after neonatal transplantation.