Neuromuscular transmission in a transgenic animal model of motor neuron disease

The transgenic mice that express a human Cu,Zn superoxide dismutase (SOD) mutation are a plausible animal model of amyotrophic lateral sclerosis (ALS) in familial form. To explore the effects of the SOD mutation on motor nerve terminal (MNT) function, we studied neuromuscular transmission in mice with a mutated human SOD gene (G1H and G1L) as well as mice with the wild-type human SOD gene (N29) and normal untreated (wild-type, wt) animals for use as controls. In both G1H and G1L animals, the quantal content (m) of the neurally-evoked end-plate potentials (EPPs) was significantly increased from the values found in the corresponding control mice. The frequency and amplitude of the spontaneously occurring miniature end-plate potentials (MEPPs) were not significantly different, however. This finding is interpreted as indicating that calcium entry into the MNT, presumably mediated by the voltage-dependent calcium channels, is significantly increased by the mutation. This is consistent with the hypothesis that the Ca ²⁺-mediated neurotoxicity causes degeneration of motor neurons in this disorder.