Figure 8. A model encapsulating the postnatal requirement for the SMN protein in the murine model.

The requirement for the protein is adequately met by 1 or more SMN1 copies or SMN2 copies that, between them, express equivalent levels of the protein. This requirement is at its greatest during the neonatal period encompassing NMJ refinement and maturation. It eventually falls by approximately P20, a time point defined by the establishment of the fully mature neuromuscular synapse (see photomicrographs), to levels that are satisfied by 2 SMN2 copies. In the approximately 3-day window prior to this time point, mice become relatively resistant to low SMN. Injury of the NMJ during aging or trauma is accompanied by a surge in demand for the protein, specifically in tissues of the neuromuscular system, which is not adequately met by 2 SMN2 copies. The enhanced requirement appears to peak as the NMJ matures and brings about, in SMN-depleted mutants, an inability to fully repair the neuromuscular synapse. Thus, SMN is thought to play 2 related roles at the neuromuscular synapse — its initial maturation and its continued maintenance. Note: figure not drawn to scale.