Nerve grafts in the Trembler mouse. An electrophysiological and histological study

Sciatic nerve grafts were inserted from normal BALB C mice into Trembler mice which have a dominantly inherited hypertrophic neuropathy. The Trembler gene had been bred onto a BALB C mouse background so that the nerve grafts were performed between isogeneic animals and no immunosuppressive agent was necessary to prevent nerve rejection. The normal Schwann cells of the donor mice survived and produced normal myelin sheaths around the Trembler axons which traversed the grafted segment. The proximal and distal segments remained poorly myelinated. Within the normally myelinated graft the mean axon area was significantly greater than that within the proximal segment, even though the graft contained axonal sprouts. Electrophysiological studies were performed and motor conduction velocity calculated across the graft, and across the proximal and distal segments. Whereas the mean conduction velocity across the demyelinated Trembler nerve in the proximal segment was 2.6 m/s the mean value across the nerve graft was 31.3 m/s, a value approximately 75% that of normal mice. These findings provide confirmatory evidence that the defect responsible for this demyelinating neuropathy resides within the Schwann cell and illustrates the importance of Schwann cell-axon interdependence.