NEUROMUSCULAR FUNCTION IMPAIRMENT IS NOT CAUSED BY MOTOR-NEURON LOSS IN FALS MICE - AN ELECTROMYOGRAPHIC STUDY

DOMINANT mutations of human Cu/Zn superoxide dismutase (SOD1) are foun d in about 20% of patients with familial amyotrophic lateral sclerosis (FALS). A transgenic mouse model of FALS (FALS(G93A) mice) has been g enerated by overexpression of a mutated form of SOD1. Using electromyo graphy we first show that FALS(G93A) mice suffer from motoneurone dysf unction similar to that observed in ALS patients and fullfill Lambert' s criteria for ALS. We also showed that FALS(G93A) mice demonstrate a massive loss of functional motor units starting at 47 days of age. Imp airment of motor neurone function preceeds by 6 weeks the onset of app arent clinical signs (shaking, tremor) and the beginning of motor neur one loss. Neuromuscular deficits in FALS mice do not result from moton euronal cell death but rather from loss of axonal integrity.