Ectopic expression of NCAM in skeletal muscle of transgenic mice results in terminal sprouting at the neuromuscular junction and altered structure but not function

The neuromuscular system provides an excellent model for the analysis of mo lecular interactions involved in the development and plasticity of synaptic contacts. The neural cell adhesion molecule (NCAM) is believed to be invol ved in the development and plasticity of the neuromuscular junction, in par ticular the axonal sprouting response observed in paralyzed and denervated muscle. In order to explore the role of myofiber NCAM in modulating the dif ferentiation of motor neurons, we generated transgenic mice expressing a GP I-anchored NCAM isoform that is normally found in developing and denervated muscle, under the control of a skeletal muscle-specific promoter. This res ults in the constitutive expression of NCAM at postnatal ages, a time when the endogenous mouse NCAM is absent from the myofiber. We found that a sign ificant number of neuromuscular junctions in adult transgenic animals displ ayed terminal sprouting (>20%) reminiscent of that elicited in response to cessation of neuromuscular activity. additionally, a significant increase i n the size and complexity of neuromuscular synapses as a result of extensiv e intraterminal sprouting was detected. Electrophysiological studies, howev er, revealed no significant alterations of neuromuscular transmission at th is highly efficient synapse. Sprouting in response to paralysis or followin g nerve crush was also significantly enhanced in transgenic animals. These results suggest that in this ectopic expression model NCAM can directly mod ulate synaptic structure and motor neuron-muscle interactions. The results contrast with knockout experiments of the NCAM gene, where very limited cha nges in the neuromuscular system were observed.