Abnormal myelination in transplanted Trembler mouse Schwann cells

Abstract

AXON and Schwann cell interdependence has received increasing attention in recent years^1,2. In normal nerves, axons influence Schwann cell proliferation^3,4 and myelin formation^5–8. These interactions may also be important in peripheral nerve disorders. Indeed, it has been suggested that in certain neuropathies, it is an axonal abnormality which is responsible for the failure of Schwann cells to maintain normal myelin^9,10. An experimental approach to this question has become possible with the demonstration that, in nerve grafts from normal animals, Schwann cells which originate in donor nerves ensheath and myelinate axons arising from nerve cells in the host^6,8,11. This demonstration of the feasibility of in vivo combinations of Schwann cells and axons, each originating from different animals, prompted the present experiments in which axons and Schwann cells from normal and abnormal mice were combined in sciatic nerve grafts. For the present study, abnormal nerves were obtained from Trembler mice (Tr)¹². These mutants have a dominantly inherited neuropathy characterised by the presence of abnormally thin myelin sheaths and slow conduction in the peripheral nerves¹³, changes which have been considered to resemble those of human hypertrophic neuropathies¹⁴.