Motor Neuron Degeneration in Mice that Express a Human Cu,Zn Superoxide Dismutase Mutation
Mark E. Gurney(Northwestern University), Haifeng Pu(Northwestern University), Arlene Y. Chiu(City Of Hope National Medical Center), Mauro C. Dal Canto(Northwestern University), Cynthia Y. Polchow(Northwestern University), Denise D. Alexander(Northwestern University), Jan Caliendo(Northwestern University), Afif Hentati(Northwestern University), Young W. Kwon(Northwestern University), Han‐Xiang Deng(Northwestern University), Wenje Chen(Northwestern University), Ping Zhai(Northwestern University), Robert Sufit(Northwestern University), Teepu Siddique(Northwestern University)
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Abstract
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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