Peripheral nerve grafts in hereditary leukodystrophic mutant mice (twitcher)

Abstract

The twitcher mouse is a mutant affected by a form of leukodystrophy which shows close similarities to human globoid cell (Krabbe''s) leukodystrophy. Transmission is by an autosomal recessive gene twi. Progressive loss of myelin sheaths from both the CNS and peripheral nervous system, and the presence of inclusion-laden macrophages are characteristic findings. Morphological features of the twitcher were described by Duchen, et al. Nerve iso- and allografting were used to determine the roles of axon and Schwann cell in a number of mouse and human nerve abnormalities. Schwann cells in a graft proliferate and become associated with regenerating host axons, which grow through the graft into the host distal stump. In the twitcher, peripheral nerve axons do not degenerate but are thinner than normal, although there is considerable axonal degeneration in the CNS. In 15 day old mutants, inclusions were found in Schwann cells associated with apparently normal myelin sheaths. Grafting experiments might show whether the phenotype of this mutant is fully expressed in the Schwann cell, or if axons are also involved. In previous experiments, survival of transplanted Schwann cells was achieved by the use of T cell-suppressed or nude mice. A twitcher nerve transplanted in immunologically unsuppressed animals reproduces all the characteristic features of leukodystrophy. Schwann cells from unaffected mice can produce normal myelin when associated with twitcher axons.