Normal development of nerve-muscle synapses in mice lacking the prion protein gene.

The expression of acetylcholine receptors (AChR) at neuromuscular synapses in skeletal muscle is regulated by innervation. Recent evidence suggests that the neurotrophic factors involved in the expression of AChR subunit genes may be related to the prion protein (PrPc), a protein of unknown function expressed primarily in neurons which, in its modified form, PrPSc, is thought to have a role in the pathogenesis of transmissible spongiform encephalopathies. We have tested for an involvement of PrPc in the neurotrophic regulation of synaptic AChRs in muscle by comparing the contents of AChR epsilon- and gamma-subunit mRNAs by Northern blot analysis and by in situ hybridization in mice with normal and with deleted PrP genes. At the protein level, AChR expression was assessed electrophysiologically. No difference was found between muscles from the two types of animals, suggesting that the neural regulation of AChR subunit expression in skeletal muscle can be mediated by factors that are not derived from the PrP gene.