Extensive multiple innervation and abnormal synaptogenesis in muscular dysgenesis (mdg/mdg) in the mouse embryo

Muscular dysgenesis (mdg) is an autosomal recessive mutation in the mouse characterized by total muscle inactivity in vivo or in vitro. The muscle fiber in the mdg/mdg diaphragm was not only morphologically abnormal but also multiply innervated; the motor innervation was very dense, showing overgrowth and sprouting. As expected at the ultrastructural level, nerve-muscle contacts were composed of dense appositions of numerous axon terminals (dense focal polyinnervation). Moreover, these mdg/mdg neuromuscular junctions, lacking post-synaptic unfolding, were immature compared to the control ones. This retarded neuromuscular junction differentiation in muscular dysgenesis may be related to considerable delay in muscle maturation and/or abnormal muscular differentiation, or to a nerve defect independent of, or causally related to, the muscular defect.