THE PERIPHERAL-NERVE AND THE NEUROMUSCULAR-JUNCTION ARE AFFECTED IN THE TENASCIN-C-DEFICIENT MOUSE

A thorough examination of the structure and plasticity of the neuromus cular system was performed in tenascin-C mutant mice deficient in tena scin-C. The study of the peripheral nerve revealed a number of abnorma l features. In the motor nerve, numerous unmyelinated and myelinated f ibers with degraded myelin were present. Schwann cell processes often enclosed degenerative terminals. Transgene (beta-galactosidase) expres sion analyzed at the ultrastructural level was found to be unequally d istributed in the mutant's neuromuscular tissues. At the NMJ, pretermi nal disorganization was prevalent. Some axon terminals exhibited abnor mal overgrowth. A surprising lack of beta-galactosidase expression at some cellular sites known to possess tenascin-C in wild type mice corr elated best with marked changes in the cytoarchitecture of the periphe ral nerve and NMJ. In some other -but not all- cellular sites which no rmally express the molecule, immunofluorescence analysis suggested the presence of significant but low levels of tenascin-C-like immunoreact ivity together with beta-galactosidase expression. Messenger RNA detec tion by RT-PCR confirmed the presence of low amounts of tenascin-C mRN A in skeletal muscle suggesting that the mice deficient in tenascin-C are not complete knock-outs of this gene, but low-expression mutants. Following in vivo injections of botulinum type-A toxin, we observed a greatly reduced sprouting response of the motor nerves in tenascin-C m utant mice. We also observed that N-CAM and beta-catenin were overexpr essed in the mutant. Our results suggest that tenascin-C is involved b oth in stabilization and in plasticity of the NMJ.