Murine globoid cell leukodystrophy: the twitcher mouse. An ultrastructural study of the kidney

Kidneys of 5- to 45-day-old twitcher mice were studied by light and electron microscopy. No abnormalities were detected with the light microscope. However, at the ultrastructural level, several types of cytoplasmic inclusions were found in epithelial cells with increasing frequency with age. The characteristic inclusions of globoid cell leukodystrophy, identical with those observed in the central nervous system, were confined to epithelial cells of the thin limbs of the loop of Henle. They were present on day 5 in epithelial cells of the thin limbs of the loop of Henle in the papillae of developing kidneys and, after day 20, became more widely distributed in both descending and ascending thin limbs of long loops and in descending thin limbs of short loops. Occasionally, these characteristic inclusions were found within the lumen. Thus, although the twitcher mouse is an authentic model of human globoid cell leukodystrophy, the massive increase in renal galactosylceramide and the finding of inclusions in the twitcher mouse's kidney contrast sharply with the lack of similar changes in man.