MOTOR-NEURONS IN CU ZN SUPEROXIDE DISMUTASE-DEFICIENT MICE DEVELOP NORMALLY BUT EXHIBIT ENHANCED CELL-DEATH AFTER AXONAL INJURY/

The discovery that some cases of familial amyotrophic lateral sclerosi s (FALS) are associated with mutations in the gene encoding Cu/Zn supe roxide dismutase (SOD1) has focused much attention on the function of SOD1 as related to motor neuron survival. Here we describe the creatio n and characterization of mice completely deficient for this enzyme. T hese animals develop normally and show no overt motor deficits by 6 mo nths in age. Histological examination of the spinal cord reveals no si gns of pathology in animals 4 months in age. However Cu/Zn SOD-deficie nt mice exhibit marked vulnerability to motor neuron loss after axonal injury. These results indicate that Cu/Zn SOD is not necessary for no rmal motor neuron development and function but is required under physi ologically stressful conditions following injury.