Defective Schwann cell function in canine inherited hypertrophic neuropathy

Segments of peripheral nerve from dogs with canine inherited hypertrophic neuropathy ( CIHN ) were transplanted to the transected sciatic nerve of immuno incompetent mice. Regenerating mouse axons penetrated the grafts and were myelinated by dog Schwann cells. In grafts collected 3 or more months after transplantation, filamentous or granular material, identical to that occurring in nerves of affected dogs, accumulated in myelinating Schwann cells. Demyelinated fibers were only rarely found in grafted segments of affected nerve. Neither filamentous accumulations nor demyelination were observed in grafts of control canine nerve. These results indicate that CIHN is associated with a defect in Schwann cell function, and the abnormal accumulations of filaments suggest that the defect may be in the cytoskeleton. The rarity of demyelination in grafts suggests that some factor in addition to the Schwann cell defect is required to precipitate myelin destruction.