Motor neuron degeneration in mice that express a human Cu, Zn superoxide dismutase mutation

ME Gurney, H Pu, AY Chiu, MC Dal Canto… - Science, 1994 - science.org
ME Gurney, H Pu, AY Chiu, MC Dal Canto, CY Polchow, DD Alexander, J Caliendo…
Science, 1994science.org
Mutations of human Cu, Zn superoxide dismutase (SOD) are found in about 20 percent of
patients with familial amyotrophic lateral sclerosis (ALS). Expression of high levels of human
SOD containing a substitution of glycine to alanine at position 93—a change that has little
effect on enzyme activity—caused motor neuron disease in transgenic mice. The mice
became paralyzed in one or more limbs as a result of motor neuron loss from the spinal cord
and died by 5 to 6 months of age. The results show that dominant, gain-of-function mutations …
Mutations of human Cu,Zn superoxide dismutase (SOD) are found in about 20 percent of patients with familial amyotrophic lateral sclerosis (ALS). Expression of high levels of human SOD containing a substitution of glycine to alanine at position 93—a change that has little effect on enzyme activity—caused motor neuron disease in transgenic mice. The mice became paralyzed in one or more limbs as a result of motor neuron loss from the spinal cord and died by 5 to 6 months of age. The results show that dominant, gain-of-function mutations in SOD contribute to the pathogenesis of familial ALS.
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