The Twitcher Mouse: an Ultrastructural Study on the Oligodendroglia

Morphological alterations of oligodendroglia were investigated in the spinal cord of the twitcher mouse, an authentic murine model of human globoid cell leukodystrophy (GLD) from day 5 to day 45 postnatal (p.n.). Typical inclusions were seen in the perikarya as well as the processes of oligodendroglia after day 10 with increasing frequency. The majority of the inclusions was non-crystalloid but rather needle-like or slender tubular in appearance. Ultrastructural features of cellular degeneration became first noticeable on days 25-30 in the oligodendroglial cytoplasm. These consisted of an increased number of microtubules and/or smooth cisterns, dispersed ribosomes, alteration of endoplasmic reticulum forming stacked lamellae or whorls, vesiculation or vacuolation of cytoplasm. The number of degenerating oligodendroglia increased in the older twitcher mice, so did the degenerating myelin sheath. However, even on day 45, when globoid cells became conspicuous in subpial and perivascular regions, many oligodendroglia and myelin sheaths were still well preserved. These observations suggested that oligodendroglial degeneration resulted in the degeneration of myelin sheaths but globoid cells appeared even before morphological evidence of myelin degeneration, presumably in response to the biochemical alterations resulted from the deficiency of galactosylceramidase.