Demyelination in the spinal cord of murine globoid cell leukodystrophy (the twitcher mouse).

Chronologic events of demyelination were investigated in the spinal cord of the twitcher mouse, an authentic murine model of human globoid cell leukodystrophy (GLD) from 5 to 45 days postnatal. There was very little evidence of myelin degeneration before day 25 although clustered or scattered globoid cells were already noted in the dorsal columns and intramedullary portion of the ventral roots. Globoid cells contained typical cytoplasmic inclusions and in those which were found adjacent to degenerating myelin and naked axons, myelin debris were conspicuous in their cytoplasm. Vesiculation of myelin and a feature of globoid cells stripping myelin lamellae were noted in the area of demyelination. Myelin and oligodendroglial degeneration became pronounced throughout the spinal white matter after day 40 but globoid cells tended to be more concentrated in the dorsal columns. Our observations suggest that the emergence of globoid cells in GLD is in response to the changes in biochemical environment (i.e., excessive presence of galactosylceramide in the tissue?), and these cells appear to have a role as phagocytic cells in removing myelin lamellae.