Nerve terminal degeneration is independent of muscle fiber genotype in SOD1 mice.

Background: Motor neuron degeneration in SOD1(G93A) transgenic mice begins at the nerve terminal. Here we examine whether this degeneration depends on expression of mutant SOD1 in muscle fibers.

Methodology/principal Findings: Hindlimb muscles were transplanted between wild-type and SOD1(G93A) transgenic mice and the innervation status of neuromuscular junctions (NMJs) was examined after 2 months. The results showed that muscles from SOD1(G93A) mice did not induce motor terminal degeneration in wildtype mice and that muscles from wildtype mice did not prevent degeneration in SOD1(G93A) transgenic mice. Control studies demonstrated that muscles transplanted from SOD1(G93A) mice continued to express mutant SOD1 protein. Experiments on wildtype mice established that the host supplied terminal Schwann cells (TSCs) at the NMJs of transplanted muscles.

Conclusions/significance: These results indicate that expression of the mutant protein in muscle is not needed to cause motor terminal degeneration in SOD1(G93A) transgenic mice and that a combination of motor terminals, motor axons and Schwann cells, all of which express mutant protein may be sufficient.