MODULATION OF AXON DIAMETER AND NEUROFILAMENTS BY HYPOMYELINATING SCHWANN-CELLS IN TRANSGENIC MICE

Studies of peripheral nerves in two different lines of hypomyelinating transgenic mice support the hypothesis that myelinating Schwann cells exert a significant influence on key biological properties of axons. The mice contain transgenes combining the peripheral myelin protein ze ro gene (P-0) promoter and either the diphtheria toxin A chain gene pr oduct or the SV40 (simian virus 40) large T antigen. The consequences of peripheral nerve hypomyelination on axon diameter, neurofilament (N F) density, and NF phosphorylation were analyzed. The sciatic nerves o f the P-0 diphtheria toxin A transgenic mice (DT) evidenced the most s evere hypomyelination, and this was associated with a dramatic decreas e in NF phosphorylation plus a marked increase in NF density. In contr ast, the sciatic nerves in the P-0 SV40 large T antigen transgenic mic e (SV40) were not as severely hypomyelinated and there was a milder de crease in NF phosphorylation plus a more modest increase in NF density . Further, the sciatic nerves in both lines evidenced a decrease in ax onal caliber without any change in NF content. Taken together, these s tudies provide strong evidence indicating that myelinating Schwann cel ls exert a significant influence on axon caliber by modulating NF phos phorylation and NF packing density in the axons of peripheral nerves. Thus, key biological properties of axons are modulated by signals tran smitted from myelinating Schwann cells to axons of peripheral nerves.