The pathogenesis of globoid cell leucodystrophy in peripheral nerve of the mouse mutant twitcher.

The twitcher mouse is affected by a disease with pathological features resembling those of human globoid cell leucodystrophy (Krabbe's disease): it also has an identical enzyme deficiency. The progress of the disease has been studied in peripheral nerves. Myelin sheaths develop normally until about the 15th day when the rate of myelination declines. Demyelination, first affecting paranodal regions is seen from the 10th-11th day before clinical signs appear. Krabbe-type inclusions are seen in macrophages and Schwann cells a few days later. Demyelination becomes extensive with increasing age, affecting fibres of all sizes, and axons rapidly remyelinate. Axons are not involved but quantitative studies show that they remain smaller than normal. Changes in twitcher nerves are compared to those in the neuropathy in human Krabbe's disease.